Details of the Researcher

PHOTO

Tomohiko Taguchi
Section
Graduate School of Life Sciences
Job title
Professor
Degree

  • 博士（理学）（東京大学）

  • 修士（理学）（東京大学）

e-Rad No.
10300881

Research History 2

  • 2018/04 - Present
    東北大学大学院　生命科学研究科　教授

  • 2011/04 - 2018/03
    東京大学大学院　薬学系研究科　特任准教授

Education 5

  • The University of Tokyo　Graduate School of Science　Department of Biophysics and Biochemistry

    1994/04 - 1997/03

  • The University of Tokyo　Graduate School of Science　Department of Biophysics and Biochemistry

    1992/04 - 1994/03

  • The University of Tokyo　Faculty of Science　Department of Biophysics and Biochemistry

    1990/04 - 1992/03

  • 東京大学理科I類

    1988/04 - 1990/03

  • 兵庫県立神戸高等学校

    1985/04 - 1988/03

Committee Memberships 7

  • 一般社団法人 日本細胞生物学会　理事

    2022/06 - Present

  • 一般社団法人 日本細胞生物学会　代議員

    2018/06 - Present

  • 日本脂質生化学会　幹事

    2019/01 - 2026/12

  • 公益社団法人 日本生化学会　「生化学」誌企画委員

    2020/07 - 2024/12

  • 一般社団法人 日本細胞生物学会　常任編集委員

    2017/01 - 2024/12

  • 日本生化学会　JB編集委員会 編集参与

    2018/03 - 2019/12

  • 国立研究開発法人日本医療研究開発機構 医療研究開発革新基盤創成事業（AMED CiCLE 事業)　技術アドバイザー

    2018/03 - 2019/03

Show all ︎Show first 5

Professional Memberships 4

  • 日本免疫不全・自己炎症学会

  • JAPAN SOCIETY FOR CELL BIOLOGY

  • THE JAPANESE CONFERENCE ON THE BIOCHEMISTRY OF LIPIDS

  • THE JAPANESE BIOCHEMICAL SOCIETY

Research Interests 8

  • signalling

  • endosomes

  • membrane traffic

  • innate immunity

  • phospholipids

  • organelles

  • Biochemistry

  • Cell Biology

Research Areas 1

  • Life sciences / Cell biology /

Papers 103

  1. A quantitative method to monitor STING degradation with dual-luciferase reporters.

    Tsumugi Shoji, Kanako Sato, Ayumi Shinojima, Shogo Koide, Ruri Shindo, Kazune Hongo, Kojiro Mukai, Yoshihiko Kuchitsu, Tomohiko Taguchi

    Cell structure and function　2025/04/19

    DOI： 10.1247/csf.25011 　

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    Stimulator of interferon genes (STING) triggers the type I interferon and inflammatory responses against a variety of DNA pathogens, which is essential to limiting viral infection and replication. STING activates the downstream kinase TBK1 at the trans-Golgi network (TGN) and is degraded at lysosomes through a process called lysosomal microautophagy. Impaired STING targeting to lysosomes results in the prolonged inflammatory signal, which may be associated with a variety of neurodegenerative and autoinflammatory diseases. Thus, development of methods to quantify STING degradation helps understand the mechanism of lysosomal microautophagy and its related diseases. Here we report a quantitative method to monitor STING degradation with two luciferases, firefly luciferase (FLuc) and Nanoluciferase (NLuc). The expression plasmid is composed of FLuc, a P2A self-cleavage site, and NLuc-tagged STING. FLuc intensity reflects the total amount of translated protein, serving as an internal control, while NLuc intensity corresponds to the amount of STING. Comparison of the NLuc/FLuc ratio after STING stimulation reported the kinetics of decay of STING levels in live cells. This method should provide a useful complement to western blotting and fluorescence- activated cell sorter (FACS) analysis presently used to monitor STING degradation.Key words: Innate immunity, STING, membrane traffic, lysosomal degradation, luciferase.

  2. Innate immune signals triggered on organelle membranes. International-journal

    Yoshihiko Kuchitsu, Tomohiko Taguchi

    Journal of biochemistry　2025/04/08

    DOI： 10.1093/jb/mvaf016 　

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    Our body is constantly exposed to pathogens, and equipped with a highly elaborate immune system to fight against invading pathogens. The first line of defense is the innate immune system. It has evolved to detect conserved microbial molecular patterns, dubbed pathogen-associated molecular patterns (PAMPs), through pattern recognition receptors (PRRs). The binding of PRRs to PAMPs activates intracellular signalling cascades that lead to the expression of proinflammatory cytokines, type I interferons, and other antiviral proteins that all coordinate the elimination of pathogens and infected cells. PRRs can be classified as transmembrane receptors, including Toll-like receptors (TLRs) and some C-type lectin receptors (CLRs), and as cytosolic receptors including retinoic acid-inducible gene-I (RIG-I)-like receptors, nucleotide-binding domain and leucine-rich repeat-containing (NLR) proteins, and cyclic GMP-AMP (cGAMP) synthase (cGAS). Studies have revealed that innate immune signals, including the ones activated by cytosolic PRRs, are triggered on organelle membranes. Here we review the recent insights into how organelle membranes and their associated membrane lipids contribute to PRR-mediated innate immune signals.

  3. The common HAQ STING allele prevents clinical penetrance of COPA syndrome Peer-reviewed

    Noa Simchoni, Shogo Koide, Maryel Likhite, Yoshihiko Kuchitsu, Senkottuvelan Kadirvel, Christopher S. Law, Brett M. Elicker, Santosh Kurra, Margaret Mei-Kay Wong, Bo Yuan, Alice Grossi, Ronald M. Laxer, Stefano Volpi, Dilan Dissanayake, Tomohiko Taguchi, David B. Beck, Tiphanie P. Vogel, Anthony K. Shum

    Journal of Experimental Medicine　222　(4)　2025/02/27

    Publisher: Rockefeller University Press

    DOI： 10.1084/jem.20242179 　

    ISSN： 0022-1007

    eISSN： 1540-9538

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    COPA syndrome, an autosomal-dominant inborn error of immunity, is nonpenetrant in ∼20% of individuals, with no known mediators of protection. Recent studies implicate STING in the pathogenesis of COPA syndrome. We show that the common HAQ STING allele mediates complete clinical protection. We sequenced 35 individuals with COPA mutations, 26 affected patients and 9 unaffected carriers, finding HAQ STING co-segregation with clinical nonpenetrance. Exome sequencing identified only the mutations comprising HAQ STING as variants shared by unaffected carriers and absent in patients. Experimentally, we found that HAQ STING acts dominantly to dampen COPA-dependent STING signaling. Expressing HAQ STING in patient cells rescued the molecular phenotype of COPA syndrome. Our study is the first report of a common and well-tolerated allele mediating complete clinical protection from a severe genetic disorder. Our findings redefine the diagnostic criteria for COPA syndrome, expose functional differences among STING alleles with broad scientific and clinical implications, and reveal a potential universal gene therapy approach for patients.

  4. Conjugated fatty acids drive ferroptosis through chaperone-mediated autophagic degradation of GPX4 by targeting mitochondria. International-journal Peer-reviewed

    Yusuke Hirata, Yuto Yamada, Soma Taguchi, Ryota Kojima, Haruka Masumoto, Shinnosuke Kimura, Takuya Niijima, Takashi Toyama, Ryoji Kise, Emiko Sato, Yasunori Uchida, Junya Ito, Kiyotaka Nakagawa, Tomohiko Taguchi, Asuka Inoue, Yoshiro Saito, Takuya Noguchi, Atsushi Matsuzawa

    Cell death & disease　15　(12)　884-884　2024/12/06

    DOI： 10.1038/s41419-024-07237-w 　

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    Conjugated fatty acids (CFAs) have been known for their anti-tumor activity. However, the mechanism of action remains unclear. Here, we identify CFAs as inducers of glutathione peroxidase 4 (GPX4) degradation through chaperone-mediated autophagy (CMA). CFAs, such as (10E,12Z)-octadecadienoic acid and α-eleostearic acid (ESA), induced GPX4 degradation, generation of mitochondrial reactive oxygen species (ROS) and lipid peroxides, and ultimately ferroptosis in cancer cell lines, including HT1080 and A549 cells, which were suppressed by either pharmacological blockade of CMA or genetic deletion of LAMP2A, a crucial molecule for CMA. Mitochondrial ROS were sufficient and necessary for CMA-dependent GPX4 degradation. Oral administration of an ESA-rich oil attenuated xenograft tumor growth of wild-type, but not that of LAMP2A-deficient HT1080 cells, accompanied by increased lipid peroxidation, GPX4 degradation and cell death. Our study establishes mitochondria as the key target of CFAs to trigger lipid peroxidation and GPX4 degradation, providing insight into ferroptosis-based cancer therapy.

  5. A non-toxic equinatoxin-II reveals the dynamics and distribution of sphingomyelin in the cytosolic leaflet of the plasma membrane. International-journal Peer-reviewed

    Toshiki Mori, Takahiro Niki, Yasunori Uchida, Kojiro Mukai, Yoshihiko Kuchitsu, Takuma Kishimoto, Shota Sakai, Asami Makino, Toshihide Kobayashi, Hiroyuki Arai, Yasunari Yokota, Tomohiko Taguchi, Kenichi G N Suzuki

    Scientific reports　14　(1)　16872-16872　2024/07/23

    DOI： 10.1038/s41598-024-67803-2 　

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    Sphingomyelin (SM) is a major sphingolipid in mammalian cells. SM is enriched in the extracellular leaflet of the plasma membrane (PM). Besides this localization, recent electron microscopic and biochemical studies suggest the presence of SM in the cytosolic leaflet of the PM. In the present study, we generated a non-toxic SM-binding variant (NT-EqtII) based on equinatoxin-II (EqtII) from the sea anemone Actinia equina, and examined the dynamics of SM in the cytosolic leaflet of living cell PMs. NT-EqtII with two point mutations (Leu26Ala and Pro81Ala) had essentially the same specificity and affinity to SM as wild-type EqtII. NT-EqtII expressed in the cytosol was recruited to the PM in various cell lines. Super-resolution microscopic observation revealed that NT-EqtII formed tiny domains that were significantly colocalized with cholesterol and N-terminal Lyn. Meanwhile, single molecule observation at high resolutions down to 1 ms revealed that all the examined lipid probes including NT-EqtII underwent apparent fast simple Brownian diffusion, exhibiting that SM and other lipids in the cytosolic leaflet rapidly moved in and out of domains. Thus, the novel SM-binding probe demonstrated the presence of the raft-like domain in the cytosolic leaflet of living cell PMs.

  6. Collaboration between a cis-interacting natural killer cell receptor and membrane sphingolipid is critical for the phagocyte function Peer-reviewed

    Hitomi Karyu, Takahiro Niki, Yuriko Sorimachi, Shoji Hata, Shiho Shimabukuro-Demoto, Tetsuya Hirabayashi, Kojiro Mukai, Kohji Kasahara, Keiyo Takubo, Nobuhito Goda, Koichi Honke, Tomohiko Taguchi, Hiroyuki Sorimachi, Noriko Toyama-Sorimachi

    Frontiers in Immunology　15　2024/04/24

    Publisher: Frontiers Media SA

    DOI： 10.3389/fimmu.2024.1401294 　

    eISSN： 1664-3224

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    Inhibitory natural killer (NK) cell receptors recognize MHC class I (MHC-I) in trans on target cells and suppress cytotoxicity. Some NK cell receptors recognize MHC-I in cis, but the role of this interaction is uncertain. Ly49Q, an atypical Ly49 receptor expressed in non-NK cells, binds MHC-I in cis and mediates chemotaxis of neutrophils and type I interferon production by plasmacytoid dendritic cells. We identified a lipid-binding motif in the juxtamembrane region of Ly49Q and found that Ly49Q organized functional membrane domains comprising sphingolipids via sulfatide binding. Ly49Q recruited actin-remodeling molecules to an immunoreceptor tyrosine-based inhibitory motif, which enabled the sphingolipid-enriched membrane domain to mediate complicated actin remodeling at the lamellipodia and phagosome membranes during phagocytosis. Thus, Ly49Q facilitates integrative regulation of proteins and lipid species to construct a cell type-specific membrane platform. Other Ly49 members possess lipid binding motifs; therefore, membrane platform organization may be a primary role of some NK cell receptors.

  7. STINGing organelle surface with acid Invited Peer-reviewed

    Yoshihiko Kuchitsu, Tomohiko Taguchi

    EMBO Reports　2024/03/19

    DOI： 10.1038/s44319-024-00120-x 　

  8. Single-molecule localization microscopy reveals STING clustering at the trans-Golgi network through palmitoylation-dependent accumulation of cholesterol Peer-reviewed

    Haruka Kemmoku, Kanoko Takahashi, Kojiro Mukai, Toshiki Mori, Koichiro M. Hirosawa, Fumika Kiku, Yasunori Uchida, Yoshihiko Kuchitsu, Yu Nishioka, Masaaki Sawa, Takuma Kishimoto, Kazuma Tanaka, Yasunari Yokota, Hiroyuki Arai, Kenichi G. N. Suzuki, Tomohiko Taguchi

    Nature Communications　15　(1)　2024/01/11

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1038/s41467-023-44317-5 　

    eISSN： 2041-1723

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    Abstract Stimulator of interferon genes (STING) is critical for the type I interferon response to pathogen- or self-derived DNA in the cytosol. STING may function as a scaffold to activate TANK-binding kinase 1 (TBK1), but direct cellular evidence remains lacking. Here we show, using single-molecule imaging of STING with enhanced time resolutions down to 5 ms, that STING becomes clustered at the trans-Golgi network (about 20 STING molecules per cluster). The clustering requires STING palmitoylation and the Golgi lipid order defined by cholesterol. Single-molecule imaging of TBK1 reveals that STING clustering enhances the association with TBK1. We thus provide quantitative proof-of-principle for the signaling STING scaffold, reveal the mechanistic role of STING palmitoylation in the STING activation, and resolve the long-standing question of the requirement of STING translocation for triggering the innate immune signaling.

  9. Lysosomal microautophagy: an emerging dimension in mammalian autophagy. International-journal Peer-reviewed

    Yoshihiko Kuchitsu, Tomohiko Taguchi

    Trends in cell biology　2023/12/15

    DOI： 10.1016/j.tcb.2023.11.005 　

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    Autophagy is a self-catabolic process through which cellular components are delivered to lysosomes for degradation. There are three types of autophagy, i.e., macroautophagy, chaperone-mediated autophagy (CMA), and microautophagy. In macroautophagy, a portion of the cytoplasm is wrapped by the autophagosome, which then fuses with lysosomes and delivers the engulfed cytoplasm for degradation. In CMA, the translocation of cytosolic substrates to the lysosomal lumen is directly across the limiting membrane of lysosomes. In microautophagy, lytic organelles, including endosomes or lysosomes, take up a portion of the cytoplasm directly. Although macroautophagy has been investigated extensively, microautophagy has received much less attention. Nonetheless, it has become evident that microautophagy plays a variety of cellular roles from yeast to mammals. Here we review the very recent updates of microautophagy. In particular, we focus on the feature of the degradative substrates and the molecular machinery that mediates microautophagy.

  10. Membrane traffic governs the STING inflammatory signalling Invited Peer-reviewed

    Tomohiko Taguchi

    The Journal of Biochemistry　2023/11/30

    Publisher: Oxford University Press ({OUP})

    DOI： 10.1093/jb/mvad064 　

    ISSN： 0021-924X 1756-2651

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    <jats:title>Abstract</jats:title> <jats:p>The cGAS-STING innate immune pathway has recently emerged as a critical driver of inflammation in a variety of settings, such as virus infection, cellular stress and tissue damage. The pathway detects microbial and host-derived double-stranded DNA (dsDNA) in the cytosol, and triggers the production of the type I interferons through the activation of IRF3. The detailed mechanistic and biochemical understanding of the pathway has enabled the development of pharmacological agents for the treatment of chronic inflammation and cancer. STING is an endoplasmic reticulum (ER)-localized transmembrane protein. Upon emergence of cytosolic dsDNA, STING exits the ER and migrates sequentially to the Golgi, recycling endosomes and lysosomes. Importantly, the intracellular translocation of STING is essential for the activation and inactivation of the STING signalling. In this review, I summarize the recent insights into the regulators of the membrane traffic of STING and STING-associated autoinflammatory diseases.</jats:p>

  11. PPP1R12A is a recycling endosomal phosphatase that facilitates YAP activation Peer-reviewed

    Chiaki Inoue, Kojiro Mukai, Tatsuyuki Matsudaira, Jun Nakayama, Nozomu Kono, Junken Aoki, Hiroyuki Arai, Yasunori Uchida, Tomohiko Taguchi

    Scientific Reports　13　(1)　2023/11/13

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1038/s41598-023-47138-0 　

    eISSN： 2045-2322

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    Abstract Yes-associated protein (YAP) is a transcriptional coactivator that is essential for the malignancy of various cancers. We have previously shown that YAP activity is positively regulated by phosphatidylserine (PS) in recycling endosomes (REs). However, the mechanism by which YAP is activated by PS in REs remains unknown. In the present study, we examined a group of protein phosphatases (11 phosphatases) that we had identified previously as PS-proximity protein candidates. Knockdown experiments of these phosphatases suggested that PPP1R12A, a regulatory subunit of the myosin phosphatase complex, was essential for YAP-dependent proliferation of triple-negative breast cancer MDA-MB-231 cells. Knockdown of PPP1R12A increased the level of phosphorylated YAP, reduced that of YAP in the nucleus, and suppressed the transcription of CTGF (a YAP-regulated gene), reinforcing the role of PPP1R12A in YAP activation. ATP8A1 is a PS-flippase that concentrates PS in the cytosolic leaflet of the RE membrane and positively regulates YAP signalling. In subcellular fractionation experiments using cell lysates, PPP1R12A in control cells was recovered exclusively in the microsomal fraction. In contrast, a fraction of PPP1R12A in ATP8A1-depleted cells was recovered in the cytosolic fraction. Cohort data available from the Cancer Genome Atlas showed that high expression of PPP1R12A, PP1B encoding the catalytic subunit of the myosin phosphatase complex, or ATP8A1 correlated with poor prognosis in breast cancer patients. These results suggest that the “ATP8A1-PS-YAP phosphatase” axis in REs facilitates YAP activation and thus cell proliferation.

  12. Class B1 GPCR activation by an intracellular agonist. International-journal Peer-reviewed

    Kazuhiro Kobayashi, Kouki Kawakami, Tsukasa Kusakizako, Atsuhiro Tomita, Michihiro Nishimura, Kazuhiro Sawada, Hiroyuki H Okamoto, Suzune Hiratsuka, Gaku Nakamura, Riku Kuwabara, Hiroshi Noda, Hiroyasu Muramatsu, Masaru Shimizu, Tomohiko Taguchi, Asuka Inoue, Takeshi Murata, Osamu Nureki

    Nature　618　(7967)　1085-1093　2023/06/07

    DOI： 10.1038/s41586-023-06169-3 　

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    G protein-coupled receptors (GPCRs) generally accommodate specific ligands in the orthosteric-binding pockets. Ligand binding triggers a receptor allosteric conformational change that leads to the activation of intracellular transducers, G proteins and β-arrestins. Because these signals often induce adverse effects, the selective activation mechanism for each transducer must be elucidated. Thus, many orthosteric-biased agonists have been developed, and intracellular-biased agonists have recently attracted broad interest. These agonists bind within the receptor intracellular cavity and preferentially tune the specific signalling pathway over other signalling pathways, without allosteric rearrangement of the receptor from the extracellular side1-3. However, only antagonist-bound structures are currently available1,4-6, and there is no evidence to support that biased agonist binding occurs within the intracellular cavity. This limits the comprehension of intracellular-biased agonism and potential drug development. Here we report the cryogenic electron microscopy structure of a complex of Gs and the human parathyroid hormone type 1 receptor (PTH1R) bound to a PTH1R agonist, PCO371. PCO371 binds within an intracellular pocket of PTH1R and directly interacts with Gs. The PCO371-binding mode rearranges the intracellular region towards the active conformation without extracellularly induced allosteric signal propagation. PCO371 stabilizes the significantly outward-bent conformation of transmembrane helix 6, which facilitates binding to G proteins rather than β-arrestins. Furthermore, PCO371 binds within the highly conserved intracellular pocket, activating 7 out of the 15 class B1 GPCRs. Our study identifies a new and conserved intracellular agonist-binding pocket and provides evidence of a biased signalling mechanism that targets the receptor-transducer interface.

  13. STING signalling is terminated through ESCRT-dependent microautophagy of vesicles originating from recycling endosomes. International-journal Peer-reviewed

    Yoshihiko Kuchitsu, Kojiro Mukai, Rei Uematsu, Yuki Takaada, Ayumi Shinojima, Ruri Shindo, Tsumugi Shoji, Shiori Hamano, Emari Ogawa, Ryota Sato, Kensuke Miyake, Akihisa Kato, Yasushi Kawaguchi, Masahiko Nishitani-Isa, Kazushi Izawa, Ryuta Nishikomori, Takahiro Yasumi, Takehiro Suzuki, Naoshi Dohmae, Takefumi Uemura, Glen N Barber, Hiroyuki Arai, Satoshi Waguri, Tomohiko Taguchi

    Nature cell biology　25　(3)　453-466　2023/03

    DOI： 10.1038/s41556-023-01098-9 　

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    Stimulator of interferon genes (STING) is essential for the type I interferon response against a variety of DNA pathogens. Upon emergence of cytosolic DNA, STING translocates from the endoplasmic reticulum to the Golgi where STING activates the downstream kinase TBK1, then to lysosome through recycling endosomes (REs) for its degradation. Although the molecular machinery of STING activation is extensively studied and defined, the one underlying STING degradation and inactivation has not yet been fully elucidated. Here we show that STING is degraded by the endosomal sorting complexes required for transport (ESCRT)-driven microautophagy. Airyscan super-resolution microscopy and correlative light/electron microscopy suggest that STING-positive vesicles of an RE origin are directly encapsulated into Lamp1-positive compartments. Screening of mammalian Vps genes, the yeast homologues of which regulate Golgi-to-vacuole transport, shows that ESCRT proteins are essential for the STING encapsulation into Lamp1-positive compartments. Knockdown of Tsg101 and Vps4, components of ESCRT, results in the accumulation of STING vesicles in the cytosol, leading to the sustained type I interferon response. Knockdown of Tsg101 in human primary T cells leads to an increase the expression of interferon-stimulated genes. STING undergoes K63-linked ubiquitination at lysine 288 during its transit through the Golgi/REs, and this ubiquitination is required for STING degradation. Our results reveal a molecular mechanism that prevents hyperactivation of innate immune signalling, which operates at REs.

  14. A non-nucleotide agonist that binds covalently to cysteine residues of STING Peer-reviewed

    Kentaro Matsumoto, Shenwei Ni, Hiroyuki Arai, Takashi Toyama, Yoshiro Saito, Takehiro Suzuki, Naoshi Dohmae, Kojiro Mukai, Tomohiko Taguchi

    Cell Structure and Function　48　(1)　59-70　2023/02

    Publisher: Japan Society for Cell Biology

    DOI： 10.1247/csf.22085 　

    ISSN： 0386-7196

    eISSN： 1347-3700

  15. FilGAP, a GAP for Rac1, down-regulates invadopodia formation in breast cancer cells Peer-reviewed

    Koji Saito, Sakino Ozawa, Yosuke Chiba, Ruri Takahashi, Ryoya Ogomori, Kojiro Mukai, Tomohiko Taguchi, Hiroyasu Hatakeyama, Yasutaka Ohta

    Cell Structure and Function　2023

    Publisher: Japan Society for Cell Biology

    DOI： 10.1247/csf.23032 　

    ISSN： 0386-7196

    eISSN： 1347-3700

  16. TLR7/8 stress response drives histiocytosis in SLC29A3 disorders International-journal Peer-reviewed

    Takuma Shibata, Ryota Sato, Masato Taoka, Shin-Ichiroh Saitoh, Mayumi Komine, Kiyoshi Yamaguchi, Susumu Goyama, Yuji Motoi, Jiro Kitaura, Kumi Izawa, Yoshio Yamauchi, Yumiko Tsukamoto, Takeshi Ichinohe, Etsuko Fujita, Ryosuke Hiranuma, Ryutaro Fukui, Yoichi Furukawa, Toshio Kitamura, Toshiyuki Takai, Arinobu Tojo, Mamitaro Ohtsuki, Umeharu Ohto, Toshiyuki Shimizu, Manabu Ozawa, Nobuaki Yoshida, Toshiaki Isobe, Eicke Latz, Kojiro Mukai, Tomohiko Taguchi, Kensuke Miyake

    The Journal of experimental medicine　220　(9)　2022/10/27

    Publisher: Cold Spring Harbor Laboratory

    DOI： 10.1101/2022.10.27.513971 　

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    Abstract SLC29A3, also known as ENT3, is a lysosomal transmembrane protein that transports nucleosides from the lysosomes to the cytoplasm1. Loss-of-function mutations inSLC29A3cause lysosomal nucleoside storage and histiocytosis: phagocyte accumulation in multiple organs2,3. However, little is known about the mechanism through which lysosomal nucleoside storage drives histiocytosis. Herein, histiocytosis inSlc29a3−/−mice was demonstrated to depend on TLR7, which senses a combination of nucleosides and oligoribonucleotides4,5. TLR7 responded to lysosomal nucleoside storage and enhanced proliferation of Ly6ChiCX3CR1lowimmature monocytes and their maturation into Ly6Clowphagocytes inSlc29a3−/−mice. Because accumulated nucleosides primarily originated from cell corpse phagocytosis, TLR7 in immature monocytes recognized nucleoside storage as lysosomal stress and increased phagocyte numbers. This non-inflammatory compensatory response is referred to as the TLR7 stress response where Syk, GSK3β, β-catenin, and mTORC1 serve as downstream signalling molecules. In SLC29A3 disorders, histiocytosis accompanies inflammation6,7. Nucleoside storage failed to induce pro-inflammatory cytokine production inSlc29a3−/−mice, but enhanced ssRNA-dependent pro-inflammatory cytokine production in Ly6Chiclassical monocytes and peripheral macrophages, not proliferating immature monocytes. Patient-derived monocytes harbouring G208RSLC29A3mutation showed higher survival and proliferation in the presence of M-CSF and produced larger amounts of IL-6 upon ssRNA stimulation than did those derived from healthy subjects. A TLR8 antagonist inhibited the survival/proliferation of patient-derived macrophages. These results demonstrated that TLR7/8 responses to lysosomal nucleoside stress drive SLC29A3 disorders.

  17. Pyrinインフラマソームの過剰活性化を原因とする新たな自己炎症性疾患 CDC42 C-term病の病態解析

    伊佐 真彦[西谷], 向井 康治朗, 本田 吉孝, 仁平 寛士, 田中 孝之, 柴田 洋史, 日衛嶋 栄太郎, 井澤 和司, 川崎 ゆり, 大澤 光次郎, 堅田 有宇, 小野寺 幸子, 渡邉 達也, 呉 繁夫, 滝田 順子, 小原 收, 齋藤 潤, 西小森 隆太, 田口 友彦, 笹原 洋二, 八角 高裕

    日本免疫不全・自己炎症学会雑誌　1　(2)　70-70　2022/09

    Publisher: (一社)日本免疫不全・自己炎症学会

    eISSN： 2435-7693

  18. Pyrinインフラマソームの過剰活性化を原因とする新たな自己炎症性疾患 CDC42 C-term病の病態解析

    伊佐 真彦[西谷], 向井 康治朗, 本田 吉孝, 仁平 寛士, 田中 孝之, 柴田 洋史, 日衛嶋 栄太郎, 井澤 和司, 川崎 ゆり, 大澤 光次郎, 堅田 有宇, 小野寺 幸子, 渡邉 達也, 呉 繁夫, 滝田 順子, 小原 收, 齋藤 潤, 西小森 隆太, 田口 友彦, 笹原 洋二, 八角 高裕

    日本免疫不全・自己炎症学会雑誌　1　(2)　70-70　2022/09

    Publisher: (一社)日本免疫不全・自己炎症学会

    eISSN： 2435-7693

  19. Trapping of CDC42 C-terminal variants in the Golgi drives pyrin inflammasome hyperactivation. International-journal Peer-reviewed

    Masahiko Nishitani-Isa, Kojiro Mukai, Yoshitaka Honda, Hiroshi Nihira, Takayuki Tanaka, Hirofumi Shibata, Kumi Kodama, Eitaro Hiejima, Kazushi Izawa, Yuri Kawasaki, Mitsujiro Osawa, Yu Katata, Sachiko Onodera, Tatsuya Watanabe, Takashi Uchida, Shigeo Kure, Junko Takita, Osamu Ohara, Megumu K Saito, Ryuta Nishikomori, Tomohiko Taguchi, Yoji Sasahara, Takahiro Yasumi

    The Journal of experimental medicine　219　(6)　e20211889　2022/06/06

    DOI： 10.1084/jem.20211889 　

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    Mutations in the C-terminal region of the CDC42 gene cause severe neonatal-onset autoinflammation. Effectiveness of IL-1β-blocking therapy indicates that the pathology involves abnormal inflammasome activation; however, the mechanism underlying autoinflammation remains to be elucidated. Using induced-pluripotent stem cells established from patients carrying CDC42R186C, we found that patient-derived cells secreted larger amounts of IL-1β in response to pyrin-activating stimuli. Aberrant palmitoylation and localization of CDC42R186C protein to the Golgi apparatus promoted pyrin inflammasome assembly downstream of pyrin dephosphorylation. Aberrant subcellular localization was the common pathological feature shared by CDC42 C-terminal variants with inflammatory phenotypes, including CDC42*192C*24 that also localizes to the Golgi apparatus. Furthermore, the level of pyrin inflammasome overactivation paralleled that of mutant protein accumulation in the Golgi apparatus, but not that of the mutant GTPase activity. These results reveal an unexpected association between CDC42 subcellular localization and pyrin inflammasome activation that could pave the way for elucidating the mechanism of pyrin inflammasome formation.

  20. Specific association of TBK1 with the trans-Golgi network following STING stimulation Peer-reviewed

    Haruka Kemmoku, Yoshihiko Kuchitsu, Kojiro Mukai, Tomohiko Taguchi

    Cell Structure and Function　47　(1)　19-30　2022/03/08

    Publisher: Japan Society for Cell Biology

    DOI： 10.1247/csf.21080 　

    ISSN： 0386-7196

    eISSN： 1347-3700

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    Stimulator of interferon genes (STING) is essential for the type I interferon response induced by microbial DNA or self-DNA leaked from mitochondria/nuclei. In response to the emergence of such DNAs in the cytosol, STING relocates from the endoplasmic reticulum (ER) to the Golgi, and activates TANK-binding kinase 1 (TBK1), a cytosolic kinase essential for the activation of STING-dependent downstream signalling. To understand at which subcellular compartments TBK1 becomes associated with STING, we generated cells stably expressing fluorescent protein-tagged STING (mNeonGreen-STING) and TBK1 (TBK1-mScarletI). We found that after STING stimulation, TBK1 became associated with the trans-Golgi network (TGN), not the other parts of the Golgi. STING variants that constitutively induce the type I interferon response have been identified in patients with autoinflammatory diseases named "STING-associated vasculopathy with onset in infancy (SAVI)". Even in cells expressing these constitutively active STING variants, TBK1 was found to be associated with TGN, not the other parts of the Golgi. These results suggest that TGN acts as a specific platform where STING associates with and activates TBK1.Key words: the Golgi, membrane traffic, innate immunity, STING.

  21. Autoinflammatory and neurodegenerative diseases caused by constitutive activation of STING Peer-reviewed

    Kuchitsu Yoshihiko, Mukai Kojiro, Taguchi Tomohiko

    JSIAD Journal　1　(1)　24-34　2022/01/17

    Publisher: Japanese Society for Immunodeficiency and Autoinflammatory Diseases

    DOI： 10.34563/jsiadjournal.1.1_24 　

    eISSN： 2435-7693

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    Cyclic GMP-AMP （cGAMP） synthase （cGAS） and stimulator of interferon genes （STING） are the two key molecules that trigger type I interferon reponse upon the emergence of cytosolic “non-self DNA”，such as the one from DNA viruses. Recent studies have shown that this pathway is also activated with “self-DNA” leaked out from the nucleus or mitochondria. Moreover，the cGAS-STING pathway is revealed to be associated with various autoinflammatory，autoimmune，and neurodegenerative diseases. In this review，we particularly focus on emerging issues regarding the regulation of STING activity by membrane traffic. The dysregulated membrane traffic of STING are recently shown by us and others to underly the pathogenesis of autoinflammatory diseases，SAVI （STING-associated vasculopathy with onset in infancy） and COPA （a monogenic autoinflammatory disease caused by missense mutations of coatomer protein complex subunit α （α-COP））.

  22. Quick and Mild Isolation of Intact Lysosomes Using Magnetic-Plasmonic Hybrid Nanoparticles. International-journal Peer-reviewed

    The Son Le, Mari Takahashi, Noriyoshi Isozumi, Akio Miyazato, Yuichi Hiratsuka, Kazuaki Matsumura, Tomohiko Taguchi, Shinya Maenosono

    ACS nano　16　(1)　885-896　2022/01/03

    DOI： 10.1021/acsnano.1c08474 　

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    Rapid and efficient isolation of intact lysosomes is necessary to study their functions and metabolites by proteomic analysis. We developed a swift and robust nanoparticle-based magnetic separation method in which magnetic-plasmonic hybrid nanoparticles (MPNPs) conjugated with amino dextran (aDxt) were targeted to the lumen of lysosomes via the endocytosis pathway. For well-directed magnetic separation of the lysosomes, it is important to trace the intracellular trafficking of the aDxt-conjugated MPNPs (aDxt-MPNPs) in the endocytosis pathway. Therefore, we analyzed the intracellular transport process of the aDxt-MPNPs by investigating the time-dependent colocalization of plasmonic scattering of aDxt-MPNPs and immunostained marker proteins of organelles using the threshold Manders' colocalization coefficient (Rt). Detailed analysis of time variations of Rt for early and late endosomes and lysosomes allowed us to derive the transport kinetics of aDxt-MPNPs in a cell. After confirming the incubation time required for sufficient accumulation of aDxt-MPNPs in lysosomes, the lysosomes were magnetically isolated as intact as possible. By varying the elapsed time from homogenization to complete isolation of lysosomes (tdelay) and temperature (T), the influences of tdelay and T on the protein composition of the lysosomes were investigated by polyacrylamide gel electrophoresis and amino acid analysis. We found that the intactness of lysosomes could become impaired quite quickly, and to isolate lysosomes as intact as possible with high purity, tdelay = 30 min and T = 4 °C were optimal settings.

  23. PI4P/PS countertransport by ORP10 at ER-endosome membrane contact sites regulates endosome fission. International-journal Peer-reviewed

    Asami Kawasaki, Akiko Sakai, Hiroki Nakanishi, Junya Hasegawa, Tomohiko Taguchi, Junko Sasaki, Hiroyuki Arai, Takehiko Sasaki, Michihiro Igarashi, Fubito Nakatsu

    The Journal of cell biology　221　(1)　2022/01/03

    DOI： 10.1083/jcb.202103141 　

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    Membrane contact sites (MCSs) serve as a zone for nonvesicular lipid transport by oxysterol-binding protein (OSBP)-related proteins (ORPs). ORPs mediate lipid countertransport, in which two distinct lipids are transported counterdirectionally. How such lipid countertransport controls specific biological functions, however, remains elusive. We report that lipid countertransport by ORP10 at ER-endosome MCSs regulates retrograde membrane trafficking. ORP10, together with ORP9 and VAP, formed ER-endosome MCSs in a phosphatidylinositol 4-phosphate (PI4P)-dependent manner. ORP10 exhibited a lipid exchange activity toward its ligands, PI4P and phosphatidylserine (PS), between liposomes in vitro, and between the ER and endosomes in situ. Cell biological analysis demonstrated that ORP10 supplies a pool of PS from the ER, in exchange for PI4P, to endosomes where the PS-binding protein EHD1 is recruited to facilitate endosome fission. Our study highlights a novel lipid exchange at ER-endosome MCSs as a nonenzymatic PI4P-to-PS conversion mechanism that organizes membrane remodeling during retrograde membrane trafficking.

  24. The activity of disease-causative STING variants can be suppressed by wild-type STING through heterocomplex formation. International-journal Peer-reviewed

    Ruri Shindo, Yoshihiko Kuchitsu, Kojiro Mukai, Tomohiko Taguchi

    Frontiers in cell and developmental biology　10　1037999-1037999　2022

    DOI： 10.3389/fcell.2022.1037999 　

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    Stimulator of interferon genes (STING) is essential for the type I interferon response induced by microbial DNA from viruses or self-DNA from mitochondria/nuclei. Recently, gain-of-function mutations in STING have been identified in patients with STING-associated vasculopathy with onset in infancy (SAVI). The SAVI patients exhibit complex systemic vascular inflammation and interstitial lung disease, resulting in pulmonary fibrosis and respiratory failure. SAVI mouse models have recently developed, harbouring common SAVI mutations, such as N153S and V154M, which correspond to the human N154S and V155M, respectively. Interestingly, crosses of heterozygous SAVI mice did not yield homozygous SAVI mice as of embryonic day 14, indicating that homozygous SAVI embryos were not viable and that wild-type (WT) allele would function dominantly over SAVI alleles in terms of viability. However, the molecular mechanism underlying the dominance has not been understood. In the present study, we show that STING (WT) and STING (SAVI) can form heterocomplex. The heterocomplex localized primarily in the endoplasmic reticulum (ER) and failed to reach the trans-Golgi network (TGN), where STING activates the downstream kinase TBK1. SURF4 is the essential protein functioning in the retrieval of STING from the Golgi to the ER. The amount of SURF4 bound to STING (SAVI) significantly increased in the presence of STING (WT). These results suggest that STING (WT) can suppress the activity of STING (SAVI) by tethering STING (SAVI) to the ER through heterocomplex formation. The dormant heterocomplex formation may underlie, at least in part, the dominance of STING WT allele over SAVI alleles in the STING-triggered inflammatory response.

  25. A Role of Phosphatidylserine in the Function of Recycling Endosomes Peer-reviewed

    Junya Hasegawa, Yasunori Uchida, Kojiro Mukai, Shoken Lee, Tatsuyuki Matsudaira, and Tomohiko Taguchi

    Frontiers in cell and developmental biology　9　783857　2021/12/24

    Publisher: Frontiers Media SA

    DOI： 10.3389/fcell.2021.783857 　

    eISSN： 2296-634X

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    Cells internalize proteins and lipids in the plasma membrane (PM) and solutes in the extracellular space by endocytosis. The removal of PM by endocytosis is constantly balanced by the replenishment of proteins and lipids to PM through recycling pathway. Recycling endosomes (REs) are specific subsets of endosomes. Besides the established role of REs in recycling pathway, recent studies have revealed unanticipated roles of REs in membrane traffic and cell signalling. In this review, we highlight these emerging issues, with a particular focus on phosphatidylserine (PS), a phospholipid that is highly enriched in the cytosolic leaflet of RE membranes. We also discuss the pathogenesis of Hermansky Pudlak syndrome type 2 (HPS2) that arises from mutations in the AP3B1 gene, from the point of view of dysregulated RE functions.

  26. SLC15A4 mediates M1-prone metabolic shifts in macrophages and guards immune cells from metabolic stress. International-journal Peer-reviewed

    Toshihiko Kobayashi, Dat Nguyen-Tien, Yuriko Sorimachi, Yuki Sugiura, Takehiro Suzuki, Hitomi Karyu, Shiho Shimabukuro-Demoto, Tatsuki Uemura, Tadashi Okamura, Tomohiko Taguchi, Kohjiro Ueki, Norihiro Kato, Nobuhito Goda, Naoshi Dohmae, Keiyo Takubo, Makoto Suematsu, Noriko Toyama-Sorimachi

    Proceedings of the National Academy of Sciences of the United States of America　118　(33)　2021/08/17

    Publisher: Proceedings of the National Academy of Sciences

    DOI： 10.1073/pnas.2100295118 　

    ISSN： 1091-6490

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    The amino acid and oligopeptide transporter Solute carrier family 15 member A4 (SLC15A4), which resides in lysosomes and is preferentially expressed in immune cells, plays critical roles in the pathogenesis of lupus and colitis in murine models. Toll-like receptor (TLR)7/9- and nucleotide-binding oligomerization domain-containing protein 1 (NOD1)-mediated inflammatory responses require SLC15A4 function for regulating the mechanistic target of rapamycin complex 1 (mTORC1) or transporting L-Ala-γ-D-Glu-meso-diaminopimelic acid, IL-12: interleukin-12 (Tri-DAP), respectively. Here, we further investigated the mechanism of how SLC15A4 directs inflammatory responses. Proximity-dependent biotin identification revealed glycolysis as highly enriched gene ontology terms. Fluxome analyses in macrophages indicated that SLC15A4 loss causes insufficient biotransformation of pyruvate to the tricarboxylic acid cycle, while increasing glutaminolysis to the cycle. Furthermore, SLC15A4 was required for M1-prone metabolic change and inflammatory IL-12 cytokine productions after TLR9 stimulation. SLC15A4 could be in close proximity to AMP-activated protein kinase (AMPK) and mTOR, and SLC15A4 deficiency impaired TLR-mediated AMPK activation. Interestingly, SLC15A4-intact but not SLC15A4-deficient macrophages became resistant to fluctuations in environmental nutrient levels by limiting the use of the glutamine source; thus, SLC15A4 was critical for macrophage's respiratory homeostasis. Our findings reveal a mechanism of metabolic regulation in which an amino acid transporter acts as a gatekeeper that protects immune cells' ability to acquire an M1-prone metabolic phenotype in inflammatory tissues by mitigating metabolic stress.

  27. A cell-free assay implicates a role of sphingomyelin and cholesterol in STING phosphorylation. International-journal Peer-reviewed

    Kanoko Takahashi, Takahiro Niki, Emari Ogawa, Kiku Fumika, Yu Nishioka, Masaaki Sawa, Hiroyuki Arai, Kojiro Mukai, Tomohiko Taguchi

    Scientific reports　11　(1)　11996-11996　2021/06/07

    DOI： 10.1038/s41598-021-91562-z 　

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    Stimulator of interferon genes (STING) is essential for the type I interferon response induced by microbial DNA from virus or self-DNA from mitochondria/nuclei. In response to emergence of such DNAs in the cytosol, STING translocates from the endoplasmic reticulum to the Golgi, and activates TANK-binding kinase 1 (TBK1) at the trans-Golgi network (TGN). Activated TBK1 then phosphorylates STING at Ser365, generating an interferon regulatory factor 3-docking site on STING. How this reaction proceeds specifically at the TGN remains poorly understood. Here we report a cell-free reaction in which endogenous STING is phosphorylated by TBK1. The reaction utilizes microsomal membrane fraction prepared from TBK1-knockout cells and recombinant TBK1. We observed agonist-, TBK1-, "ER-to-Golgi" traffic-, and palmitoylation-dependent phosphorylation of STING at Ser365, mirroring the nature of STING phosphorylation in vivo. Treating the microsomal membrane fraction with sphingomyelinase or methyl-β-cyclodextrin, an agent to extract cholesterol from membranes, suppressed the phosphorylation of STING by TBK1. Given the enrichment of sphingomyelin and cholesterol in the TGN, these results may provide the molecular basis underlying the specific phosphorylation reaction of STING at the TGN.

  28. Kinase activity of TBK1 is required for its binding to STING, but not for its recruitment to the Golgi

    Haruka Kemmoku, Yoshihiko Kuchitsu, Kojiro Mukai, Tomohiko Taguchi

    2021/04/27

    DOI： 10.1101/2021.04.27.441586 　

  29. Homeostatic regulation of STING by retrograde membrane traffic to the ER. International-journal Peer-reviewed

    Kojiro Mukai, Emari Ogawa, Rei Uematsu, Yoshihiko Kuchitsu, Fumika Kiku, Takefumi Uemura, Satoshi Waguri, Takehiro Suzuki, Naoshi Dohmae, Hiroyuki Arai, Anthony K Shum, Tomohiko Taguchi

    Nature communications　12　(1)　61-61　2021/01/04

    DOI： 10.1038/s41467-020-20234-9 　

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    Coat protein complex I (COP-I) mediates the retrograde transport from the Golgi apparatus to the endoplasmic reticulum (ER). Mutation of the COPA gene, encoding one of the COP-I subunits (α-COP), causes an immune dysregulatory disease known as COPA syndrome. The molecular mechanism by which the impaired retrograde transport results in autoinflammation remains poorly understood. Here we report that STING, an innate immunity protein, is a cargo of the retrograde membrane transport. In the presence of the disease-causative α-COP variants, STING cannot be retrieved back to the ER from the Golgi. The forced Golgi residency of STING results in the cGAS-independent and palmitoylation-dependent activation of the STING downstream signaling pathway. Surf4, a protein that circulates between the ER/ ER-Golgi intermediate compartment/ Golgi, binds STING and α-COP, and mediates the retrograde transport of STING to the ER. The STING/Surf4/α-COP complex is disrupted in the presence of the disease-causative α-COP variant. We also find that the STING ligand cGAMP impairs the formation of the STING/Surf4/α-COP complex. Our results suggest a homeostatic regulation of STING at the resting state by retrograde membrane traffic and provide insights into the pathogenesis of COPA syndrome.

  30. STING Operation at the ER/Golgi Interface. International-journal Invited Peer-reviewed

    Tomohiko Taguchi, Kojiro Mukai, Eiko Takaya, Ruri Shindo

    Frontiers in immunology　12　646304-646304　2021

    Publisher: Frontiers Media SA

    DOI： 10.3389/fimmu.2021.646304 　

    eISSN： 1664-3224

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    DNA is present in the nucleus and mitochondria of eukaryotic cells. There are, however, certain instances in which DNA emerges in the cytosol. The two major sources of cytosolic DNA are self DNA that is leaked out from the nucleus or mitochondria, and non-self DNA from DNA viruses. The cytosolic DNA triggers the host immune response. Recent studies have identified two key molecules, cyclic GMP-AMP (cGAMP) synthase (cGAS) and stimulator of interferon genes (STING) in this immune response. STING is an endoplasmic reticulum (ER) protein. After STING binding to cGAMP, STING exits the ER and translocates to the Golgi, where STING triggers the type I interferon- and proinflammatory responses through the activation of interferon regulatory factor 3 (IRF3) and nuclear factor-kappa B (NF-κB). STING also activates other cellular responses including cell senescence, autophagy, and cell death. In this review, we focus on emerging issues regarding the regulation of STING by membrane traffic, with a particular focus on the retrograde membrane traffic from the Golgi to the ER. The retrograde membrane traffic is recently shown by us and others to be critical for silencing the STING signaling pathway and the defect in this traffic underlies the pathogenesis of the COPA syndrome, a monogenic autoinflammatory disease caused by missense mutations of coatomer protein complex subunit α (COP-α).

  31. A defect in COPI-mediated transport of STING causes immune dysregulation in COPA syndrome. International-journal Peer-reviewed

    Zimu Deng, Zhenlu Chong, Christopher S Law, Kojiro Mukai, Frances O Ho, Tereza Martinu, Bradley J Backes, Walter L Eckalbar, Tomohiko Taguchi, Anthony K Shum

    The Journal of experimental medicine　217　(11)　2020/11/02

    Publisher: Rockefeller University Press

    DOI： 10.1084/jem.20201045 　

    ISSN： 0022-1007

    eISSN： 1540-9538

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    Pathogenic COPA variants cause a Mendelian syndrome of immune dysregulation with elevated type I interferon signaling. COPA is a subunit of coat protein complex I (COPI) that mediates Golgi to ER transport. Missense mutations of the COPA WD40 domain impair binding and sorting of proteins targeted for ER retrieval, but how this causes disease remains unknown. Given the importance of COPA in Golgi-ER transport, we speculated that type I interferon signaling in COPA syndrome involves missorting of STING. We show that a defect in COPI transport causes ligand-independent activation of STING. Furthermore, SURF4 is an adapter molecule that facilitates COPA-mediated retrieval of STING at the Golgi. Activated STING stimulates type I interferon-driven inflammation in CopaE241K/+ mice that is rescued in STING-deficient animals. Our results demonstrate that COPA maintains immune homeostasis by regulating STING transport at the Golgi. In addition, activated STING contributes to immune dysregulation in COPA syndrome and may be a new molecular target in treating the disease.

  32. SPOP is essential for DNA-protein cross-link repair in prostate cancer cells: SPOP-dependent removal of topoisomerase 2A from the topoisomerase 2A-DNA cleavage complex. International-journal Peer-reviewed

    Ryuta Watanabe, Masashi Maekawa, Miki Hieda, Tomohiko Taguchi, Noriyoshi Miura, Tadahiko Kikugawa, Takashi Saika, Shigeki Higashiyama

    Molecular biology of the cell　31　(6)　478-490　2020/03/15

    DOI： 10.1091/mbc.E19-08-0456 　

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    SPOP, speckle-type POZ protein is a substrate adaptor protein of the Cullin-3/RING ubiquitin E3 complex. The spop gene is the most commonly point mutated in human primary prostate cancers, but the pathological contribution of the SPOP mutations remains unclear. In this study, we investigated several known factors that are critical in the DNA--protein cross-link repair process. The depletion of SPOP or overexpression of a prostate cancer-associated SPOP mutant, F133V, in androgen receptor-positive prostate cancer cells increased the amount of topoisomerase 2A (TOP2A) in the nuclei together with the increased amount of γH2AX, an indication of DNA breaks. Tyrosyl-DNA phosphodiesterases (TDPs) and an endo/exonuclease MRE11 are enzymes that liberate TOP2A from the TOP2A-DNA cleavage complex, and thus is essential for the completion of the DNA repair process. We found that the amount of TDP1 and TDP2 was decreased in SPOP-depleted cells, and that of TDP2 and MRE11 was decreased in F133V-overexpressing cells. These results suggest that the F133V mutant exerts dominant-negative and gain-of-function effects in down-regulation of TDP2 and MRE11, respectively. We conclude that SPOP is involved in the DNA-protein cross-link repair process through the elimination of TOP2A from the TOP2A cleavage complex, which may contribute to the genome stability.

  33. FAM48A mediates compensatory autophagy induced by proteasome impairment. International-journal Peer-reviewed

    Yoshiyuki Arata, Ayaka Watanabe, Ryo Motosugi, Shun-Ichiro Iemura, Tohru Natsume, Kojiro Mukai, Tomohiko Taguchi, Shoshiro Hirayama, Jun Hamazaki, Shigeo Murata

    Genes to cells : devoted to molecular & cellular mechanisms　24　(8)　559-568　2019/08

    DOI： 10.1111/gtc.12708 　

    ISSN： 1356-9597

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    Maintaining protein homeostasis is central to cell survival. The ubiquitin-proteasome system and autophagy play pivotal roles in protein quality control through protein degradation. Activities of these degradative pathways are carefully orchestrated, and autophagy is up-regulated during proteasome dysfunction for cellular homeostasis. However, the mechanism by which proteasome impairment induces compensatory autophagy has remained largely elusive. Here, we show that FAM48A mediates autophagy induction during proteasome inhibition. FAM48A is degraded by the proteasome and accumulates in cells by proteasome inhibition. Knockdown of FAM48A led to defective induction of autophagy during proteasome inhibition and accompanied by defective localization of Atg9 on recycling endosomes. Our results indicate that FAM48A is a kind of sensor that is required for compensatory autophagy induction upon proteasome impairment.

  34. SNX9 determines the surface levels of integrin β1 in vascular endothelial cells: Implication in poor prognosis of human colorectal cancers overexpressing SNX9. International-journal Peer-reviewed

    Kazufumi Tanigawa, Masashi Maekawa, Takeshi Kiyoi, Jun Nakayama, Riko Kitazawa, Sohei Kitazawa, Kentaro Semba, Tomohiko Taguchi, Satoshi Akita, Motohira Yoshida, Kei Ishimaru, Yuji Watanabe, Shigeki Higashiyama

    Journal of cellular physiology　234　(10)　17280-17294　2019/08

    Publisher: Wiley

    DOI： 10.1002/jcp.28346 　

    ISSN： 0021-9541

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    Angiogenesis, the formation of new blood vessels, is involved in a variety of diseases including the tumor growth. In response to various angiogenic stimulations, a number of proteins on the surface of vascular endothelial cells are activated to coordinate cell proliferation, migration, and spreading processes to form new blood vessels. Plasma membrane localization of these angiogenic proteins, which include vascular endothelial growth factor receptors and integrins, are warranted by intracellular membrane trafficking. Here, by using a siRNA library, we screened for the sorting nexin family that regulates intracellular trafficking and identified sorting nexin 9 (SNX9) as a novel angiogenic factor in human umbilical vein endothelial cells (HUVECs). SNX9 was essential for cell spreading on the Matrigel, and tube formation that mimics in vivo angiogenesis in HUVECs. SNX9 depletion significantly delayed the recycling of integrin β1, an essential adhesion molecule for angiogenesis, and reduced the surface levels of integrin β1 in HUVECs. Clinically, we showed that SNX9 protein was highly expressed in tumor endothelial cells of human colorectal cancer tissues. High-level expression of SNX9 messenger RNA significantly correlated with poor prognosis of the patients with colorectal cancer. These results suggest that SNX9 is an angiogenic factor and provide a novel target for the development of new antiangiogenic drugs.

  35. Innate immunity signalling and membrane trafficking. International-journal Invited Peer-reviewed

    Tomohiko Taguchi, Kojiro Mukai

    Current opinion in cell biology　59　1-7　2019/08

    DOI： 10.1016/j.ceb.2019.02.002 　

    ISSN： 0955-0674

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    The mammalian innate immune system serves as the front line of the host to eliminate invading pathogens. The receptors that sense invading pathogens or the pathogen-associated molecules localized at various membrane compartments that include the plasma membrane, endosomes, and the endoplasmic reticulum. Intriguingly, growing evidence indicates that the sites of pathogen detection do not always represent the site where innate immune signal is triggered. Rather, pathogen detection often induces translocation of the receptors by membrane trafficking. Furthermore, dysregulated membrane trafficking of the receptors renders the host susceptible to infection or prone to autoinflammatory diseases. These findings underscore the critical role of membrane trafficking in the innate immunity. In this review, we highlight emerging issues regarding PRRs and membrane trafficking, with the particular focus on STING and TLR4, the activity of which is tightly regulated by membrane trafficking.

  36. Predominant localization of phosphatidylserine at the cytoplasmic leaflet of the ER, and its TMEM16K-dependent redistribution. International-journal Peer-reviewed

    Takuma Tsuji, Jinglei Cheng, Tsuyako Tatematsu, Aoi Ebata, Hiroki Kamikawa, Akikazu Fujita, Sayuri Gyobu, Katsumori Segawa, Hiroyuki Arai, Tomohiko Taguchi, Shigekazu Nagata, Toyoshi Fujimoto

    Proceedings of the National Academy of Sciences of the United States of America　116　(27)　13368-13373　2019/07/02

    DOI： 10.1073/pnas.1822025116 　

    ISSN： 0027-8424

  37. STING palmitoylation as a therapeutic target. International-journal Peer-reviewed

    Anne Louise Hansen, Kojiro Mukai, Francisco J Schopfer, Tomohiko Taguchi, Christian K Holm

    Cellular & molecular immunology　16　(3)　236-241　2019/03

    DOI： 10.1038/s41423-019-0205-5 　

    ISSN： 1672-7681

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    Gain-of-function mutations in the STING-encoding gene TMEM173 are central to the pathology of the autoinflammatory disorder STING-associated vasculopathy with onset in infancy (SAVI). Furthermore, excessive activity of the STING signaling pathway is associated with autoinflammatory diseases, including systemic lupus erythematosus and Aicardi-Goutières syndrome (AGS). Two independent studies recently identified pharmacological inhibitors of STING. Strikingly, both types of compounds are reactive nitro-containing electrophiles that target STING palmitoylation, a posttranslational modification necessary for STING signaling. As a consequence, the activation of downstream signaling molecules and the induction of type I interferons were inhibited. The compounds were effective at ameliorating inflammation in a mouse model of AGS and in blocking the production of type I interferons in primary fibroblasts from SAVI patients. This mini-review focuses on the roles of palmitoylation in STING activation and signaling and as a pharmaceutical target for drug development.

  38. Cullin-3/KCTD10 E3 complex is essential for Rac1 activation through RhoB degradation in human epidermal growth factor receptor 2-positive breast cancer cells. International-journal Peer-reviewed

    Akari Murakami, Masashi Maekawa, Katsuhisa Kawai, Jun Nakayama, Nobukazu Araki, Kentaro Semba, Tomohiko Taguchi, Yoshiaki Kamei, Yasutsugu Takada, Shigeki Higashiyama

    Cancer science　110　(2)　650-661　2019/02

    DOI： 10.1111/cas.13899 　

    ISSN： 1347-9032

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    Rho GTPase Rac1 is a central regulator of F-actin organization and signal transduction to control plasma membrane dynamics and cell proliferation. Dysregulated Rac1 activity is often observed in various cancers including breast cancer and is suggested to be critical for malignancy. Here, we showed that the ubiquitin E3 ligase complex Cullin-3 (CUL3)/KCTD10 is essential for epidermal growth factor (EGF)-induced/human epidermal growth factor receptor 2 (HER2)-dependent Rac1 activation in HER2-positive breast cancer cells. EGF-induced dorsal membrane ruffle formation and cell proliferation that depends on both Rac1 and HER2 were suppressed in CUL3- or KCTD10-depleted cells. Mechanistically, CUL3/KCTD10 ubiquitinated RhoB for degradation, another Rho GTPase that inhibits Rac1 activation at the plasma membrane by suppressing endosome-to-plasma membrane traffic of Rac1. In HER2-positive breast cancers, high expression of Rac1 mRNA significantly correlated with poor prognosis of the patients. This study shows that this novel molecular axis (CUL3/KCTD10/RhoB) positively regulates the activity of Rac1 in HER2-positive breast cancers, and our findings may lead to new treatment options for HER2- and Rac1-positive breast cancers.

  39. The binding of TBK1 to STING requires exocytic membrane traffic from the ER. International-journal Peer-reviewed

    Emari Ogawa, Kojiro Mukai, Kota Saito, Hiroyuki Arai, Tomohiko Taguchi

    Biochemical and biophysical research communications　503　(1)　138-145　2018/09/03

    Publisher: Elsevier B.V.

    DOI： 10.1016/j.bbrc.2018.05.199 　

    ISSN： 1090-2104 0006-291X

  40. Nitro-fatty acids are formed in response to virus infection and are potent inhibitors of STING palmitoylation and signaling. International-journal Peer-reviewed

    Anne Louise Hansen, Gregory J Buchan, Michael Rühl, Kojiro Mukai, Sonia R Salvatore, Emari Ogawa, Sidsel D Andersen, Marie B Iversen, Anne L Thielke, Camilla Gunderstofte, Mona Motwani, Charlotte T Møller, Andreas S Jakobsen, Katherine A Fitzgerald, Jessica Roos, Rongtuan Lin, Thorsten J Maier, Raphaela Goldbach-Mansky, Cathrine A Miner, Wei Qian, Jonathan J Miner, Rachel E Rigby, Jan Rehwinkel, Martin R Jakobsen, Hiroyuki Arai, Tomohiko Taguchi, Francisco J Schopfer, David Olagnier, Christian K Holm

    Proceedings of the National Academy of Sciences of the United States of America　115　(33)　E7768-E7775-E7775　2018/08/14

    DOI： 10.1073/pnas.1806239115 　

    ISSN： 0027-8424

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    The adaptor molecule stimulator of IFN genes (STING) is central to production of type I IFNs in response to infection with DNA viruses and to presence of host DNA in the cytosol. Excessive release of type I IFNs through STING-dependent mechanisms has emerged as a central driver of several interferonopathies, including systemic lupus erythematosus (SLE), Aicardi-Goutières syndrome (AGS), and stimulator of IFN genes-associated vasculopathy with onset in infancy (SAVI). The involvement of STING in these diseases points to an unmet need for the development of agents that inhibit STING signaling. Here, we report that endogenously formed nitro-fatty acids can covalently modify STING by nitro-alkylation. These nitro-alkylations inhibit STING palmitoylation, STING signaling, and subsequently, the release of type I IFN in both human and murine cells. Furthermore, treatment with nitro-fatty acids was sufficient to inhibit production of type I IFN in fibroblasts derived from SAVI patients with a gain-of-function mutation in STING. In conclusion, we have identified nitro-fatty acids as endogenously formed inhibitors of STING signaling and propose for these lipids to be considered in the treatment of STING-dependent inflammatory diseases.

  41. Development of a Series of Practical Fluorescent Chemical Tools To Measure pH Values in Living Samples. International-journal Peer-reviewed

    Shodai Takahashi, Yu Kagami, Kenjiro Hanaoka, Takuya Terai, Toru Komatsu, Tasuku Ueno, Masanobu Uchiyama, Ikuko Koyama-Honda, Noboru Mizushima, Tomohiko Taguchi, Hiroyuki Arai, Tetsuo Nagano, Yasuteru Urano

    Journal of the American Chemical Society　140　(18)　5925-5933　2018/05/09

    Publisher: American Chemical Society

    DOI： 10.1021/jacs.8b00277 　

    ISSN： 1520-5126 0002-7863

  42. Cullin-3 and its adaptor protein ANKFY1 determine the surface level of integrin β1 in endothelial cells. International-journal Peer-reviewed

    Masashi Maekawa, Kazufumi Tanigawa, Tomohisa Sakaue, Hiromi Hiyoshi, Eiji Kubota, Takashi Joh, Yuji Watanabe, Tomohiko Taguchi, Shigeki Higashiyama

    Biology open　6　(11)　1707-1719　2017/11/15

    DOI： 10.1242/bio.029579 　

    ISSN： 2046-6390

  43. Endosomal phosphatidylserine is critical for the YAP signalling pathway in proliferating cells. International-journal Peer-reviewed

    Tatsuyuki Matsudaira, Kojiro Mukai, Taishin Noguchi, Junya Hasegawa, Tomohisa Hatta, Shun-Ichiro Iemura, Tohru Natsume, Norio Miyamura, Hiroshi Nishina, Jun Nakayama, Kentaro Semba, Takuya Tomita, Shigeo Murata, Hiroyuki Arai, Tomohiko Taguchi

    Nature communications　8　(1)　1246-1246　2017/11/01

    DOI： 10.1038/s41467-017-01255-3 　

    ISSN： 2041-1723

  44. Magnetic Separation of Autophagosomes from Mammalian Cells Using Magnetic-Plasmonic Hybrid Nanobeads. International-journal Peer-reviewed

    Mari Takahashi, Priyank Mohan, Kojiro Mukai, Yuichi Takeda, Takeo Matsumoto, Kazuaki Matsumura, Masahiro Takakura, Hiroyuki Arai, Tomohiko Taguchi, Shinya Maenosono

    ACS omega　2　(8)　4929-4937　2017/08/31

    DOI： 10.1021/acsomega.7b00929 　

    ISSN： 2470-1343

  45. Activation of STING requires palmitoylation at the Golgi. International-journal Peer-reviewed

    Kojiro Mukai, Hiroyasu Konno, Tatsuya Akiba, Takefumi Uemura, Satoshi Waguri, Toshihide Kobayashi, Glen N Barber, Hiroyuki Arai, Tomohiko Taguchi

    Nature communications　7　11932-11932　2016/06/21

    DOI： 10.1038/ncomms11932 　

    ISSN： 2041-1723

  46. Phosphatidic acid induces EHD3-containing membrane tubulation and is required for receptor recycling. International-journal Peer-reviewed

    Yuji Henmi, Natsuko Oe, Nozomu Kono, Tomohiko Taguchi, Kohji Takei, Kenji Tanabe

    Experimental cell research　342　(1)　1-10　2016/03/01

    DOI： 10.1016/j.yexcr.2016.02.011 　

    ISSN： 0014-4827

    eISSN： 1090-2422

  47. Transport of the cholera toxin B-subunit from recycling endosomes to the Golgi requires clathrin and AP-1. International-journal Peer-reviewed

    Tatsuyuki Matsudaira, Takahiro Niki, Tomohiko Taguchi, Hiroyuki Arai

    Journal of cell science　128　(16)　3131-42　2015/08/15

    DOI： 10.1242/jcs.172171 　

    ISSN： 0021-9533

    eISSN： 1477-9137

  48. Transport through recycling endosomes requires EHD1 recruitment by a phosphatidylserine translocase. International-journal Peer-reviewed

    Shoken Lee, Yasunori Uchida, Jiao Wang, Tatsuyuki Matsudaira, Takatoshi Nakagawa, Takuma Kishimoto, Kojiro Mukai, Takehiko Inaba, Toshihide Kobayashi, Robert S Molday, Tomohiko Taguchi, Hiroyuki Arai

    The EMBO journal　34　(5)　669-88　2015/03/04

    DOI： 10.15252/embj.201489703 　

    ISSN： 0261-4189

    eISSN： 1460-2075

  49. Ag/FeCo/Ag core/shell/shell magnetic nanoparticles with plasmonic imaging capability. International-journal Peer-reviewed

    Mari Takahashi, Priyank Mohan, Akiko Nakade, Koichi Higashimine, Derrick Mott, Tsutomu Hamada, Kazuaki Matsumura, Tomohiko Taguchi, Shinya Maenosono

    Langmuir : the ACS journal of surfaces and colloids　31　(7)　2228-36　2015/02/24

    DOI： 10.1021/la5046805 　

    ISSN： 0743-7463

  50. Visualization of the heterogeneous membrane distribution of sphingomyelin associated with cytokinesis, cell polarity, and sphingolipidosis. International-journal Peer-reviewed

    Asami Makino, Mitsuhiro Abe, Motohide Murate, Takehiko Inaba, Neval Yilmaz, Françoise Hullin-Matsuda, Takuma Kishimoto, Nicole L Schieber, Tomohiko Taguchi, Hiroyuki Arai, Gregor Anderluh, Robert G Parton, Toshihide Kobayashi

    FASEB journal : official publication of the Federation of American Societies for Experimental Biology　29　(2)　477-93　2015/02

    DOI： 10.1096/fj.13-247585 　

    ISSN： 0892-6638

    eISSN： 1530-6860

  51. Retrograde Membrane Traffic and Recycling Endosome Peer-reviewed

    Yuichi Takeda, Tomohiko Taguchi

    Glycoscience: Biology and Medicine　943-948　2015/01/01

    Publisher: Springer Japan

    DOI： 10.1007/978-4-431-54841-6_47 　

  52. Endosomal lipid flippases and their related diseases. International-journal Invited Peer-reviewed

    Shoken Lee, Tomohiko Taguchi, Hiroyuki Arai

    Channels (Austin, Tex.)　9　(4)　166-8　2015

    DOI： 10.1080/19336950.2015.1062332 　

    ISSN： 1933-6950

    eISSN： 1933-6969

  53. Lipid compartmentalization in the endosome system. International-journal Peer-reviewed

    Françoise Hullin-Matsuda, Tomohiko Taguchi, Peter Greimel, Toshihide Kobayashi

    Seminars in cell & developmental biology　31　48-56　2014/07

    DOI： 10.1016/j.semcdb.2014.04.010 　

    ISSN： 1084-9521

  54. Retrograde Membrane Traffic and Recycling Endosome Peer-reviewed

    Yuichi Takeda, Tomohiko Taguchi

    Glycoscience: Biology and Medicine　1-6　2014/05

    Publisher: Springer Japan

    DOI： 10.1007/978-4-431-54836-2_47-1 　

  55. Sequential breakdown of 3-phosphorylated phosphoinositides is essential for the completion of macropinocytosis. International-journal Peer-reviewed

    Masashi Maekawa, Shimpei Terasaka, Yasuhiro Mochizuki, Katsuhisa Kawai, Yuka Ikeda, Nobukazu Araki, Edward Y Skolnik, Tomohiko Taguchi, Hiroyuki Arai

    Proceedings of the National Academy of Sciences of the United States of America　111　(11)　E978-87-E987　2014/03/18

    DOI： 10.1073/pnas.1311029111 　

    ISSN： 0027-8424

  56. Mannosyl (alpha-1,3[6?]-)-glycoprotein beta-1,4-NAcetylglucosaminyltransferase, isozyme C (putative) (MGAT4C) Peer-reviewed

    Tomohiko Taguchi

    Handbook of Glycosyltransferases and Related Genes, Second Edition　1　257-263　2014/01/01

    Publisher: Springer Japan

    DOI： 10.1007/978-4-431-54240-7_134 　

  57. Small GTPases and phosphoinositides in the regulatory mechanisms of macropinosome formation and maturation. International-journal Peer-reviewed

    Youhei Egami, Tomohiko Taguchi, Masashi Maekawa, Hiroyuki Arai, Nobukazu Araki

    Frontiers in physiology　5　374-374　2014

    DOI： 10.3389/fphys.2014.00374 　

    ISSN： 1664-042X

  58. Oxysterol-binding protein (OSBP) is required for the perinuclear localization of intra-Golgi v-SNAREs. International-journal Peer-reviewed

    Taki Nishimura, Yasunori Uchida, Rieko Yachi, Tetyana Kudlyk, Vladimir Lupashin, Takao Inoue, Tomohiko Taguchi, Hiroyuki Arai

    Molecular biology of the cell　24　(22)　3534-44　2013/11

    Publisher: American Society for Cell Biology (ASCB)

    DOI： 10.1091/mbc.E13-05-0250 　

    ISSN： 1059-1524

    eISSN： 1939-4586

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    Oxysterol-binding protein (OSBP) and OSBP-related proteins (ORPs) have been implicated in the distribution of sterols among intracellular organelles. OSBP regulates the Golgi cholesterol level, but how it relates to Golgi function is elusive. Here we report that OSBP is essential for the localization of intra-Golgi soluble vesicle N-ethylmaleimide-sensitive fusion attachment protein receptors (v-SNAREs). Depletion of OSBP by small interfering RNA causes mislocalization of intra-Golgi v-SNAREs GS28 and GS15 throughout the cytoplasm without affecting the perinuclear localization of Golgi target-SNARE syntaxin5 and reduces the abundance of a Golgi enzyme, mannosidase II (Man II). GS28 mislocalization and Man II reduction are also induced by cellular cholesterol depletion. Three domains of OSBP-an endoplasmic reticulum-targeting domain, a Golgi-targeting domain, and a sterol-binding domain-are all required for Golgi localization of GS28. Finally, GS28 mislocalization and Man II reduction in OSBP-depleted cells are largely restored by depletion of ArfGAP1, a regulator of the budding of coat protein complex (COP)-I vesicles. From these results, we postulate that Golgi cholesterol level, which is controlled by OSBP, is essential for Golgi localization of intra-Golgi v-SNAREs by ensuring proper COP-I vesicle transport.

  59. A method for determination of UDP-GlcNAc: GlcNAcβ1-6(GlcNAcβ1-2)Manα1-R [GlcNAc to Man] β1-4N-acetylglucosaminyltransferase VI activity. International-journal Peer-reviewed

    Tomohiko Taguchi, Naoyuki Taniguchi

    Methods in molecular biology (Clifton, N.J.)　1022　299-305　2013

    Publisher: Humana Press

    DOI： 10.1007/978-1-62703-465-4_22 　

    ISSN： 1064-3745

  60. SMAP2 regulates retrograde transport from recycling endosomes to the Golgi. International-journal Peer-reviewed

    Tatsuyuki Matsudaira, Yasunori Uchida, Kenji Tanabe, Shunsuke Kon, Toshio Watanabe, Tomohiko Taguchi, Hiroyuki Arai

    PloS one　8　(7)　e69145　2013

    DOI： 10.1371/journal.pone.0069145 　

    ISSN： 1932-6203

  61. [Emerging roles of intracellular phosphatidylserine (PS) in membrane traffic]. Peer-reviewed

    Tomohiko Taguchi, Hiroyuki Arai

    Seikagaku. The Journal of Japanese Biochemical Society　84　(10)　844-8　2012/10

    ISSN： 0037-1017

  62. Retromer guides STxB and CD8-M6PR from early to recycling endosomes, EHD1 guides STxB from recycling endosome to Golgi. International-journal Peer-reviewed

    Jenna E McKenzie, Brent Raisley, Xin Zhou, Naava Naslavsky, Tomohiko Taguchi, Steve Caplan, David Sheff

    Traffic (Copenhagen, Denmark)　13　(8)　1140-59　2012/08

    DOI： 10.1111/j.1600-0854.2012.01374.x 　

    ISSN： 1398-9219

  63. Subcellular localization of sphingomyelin revealed by two toxin-based probes in mammalian cells. International-journal Peer-reviewed

    Rieko Yachi, Yasunori Uchida, Bhat Hema Balakrishna, Gregor Anderluh, Toshihide Kobayashi, Tomohiko Taguchi, Hiroyuki Arai

    Genes to cells : devoted to molecular & cellular mechanisms　17　(8)　720-7　2012/08

    DOI： 10.1111/j.1365-2443.2012.01621.x 　

    ISSN： 1356-9597

  64. Impaired retrograde membrane traffic through endosomes in a mutant CHO cell defective in phosphatidylserine synthesis. International-journal Peer-reviewed

    Shoken Lee, Yasunori Uchida, Kazuo Emoto, Masato Umeda, Osamu Kuge, Tomohiko Taguchi, Hiroyuki Arai

    Genes to cells : devoted to molecular & cellular mechanisms　17　(8)　728-36　2012/08

    DOI： 10.1111/j.1365-2443.2012.01622.x 　

    ISSN： 1356-9597

  65. Structural Insights into the Phospholipid Binding Specificity of Human Evectin-2

    OKAZAKI Seiji, KATO Ryuichi, WAKATSUKI Soichi, UCHIDA Yasunori, TAGUCHI Tomohiko, ARAI Hiroyuki

    X-RAYS　54　(2)　101-106　2012/04/30

    Publisher: The Crystallographic Society of Japan

    DOI： 10.5940/jcrsj.54.101 　

    ISSN： 0369-4585

    More details Close

    Evectin-2 is a recycling endosomal protein and plays an essential role in retrograde transport from recycling endosomes to the trans-Golgi network. The pleckstrin homology (PH) domain of Evectin-2 can specifically binds to phosphatidylserine (PS), which is enriched in recycling endosomes. To elucidate the molecular mechanism how it specifically binds to PS, we solved the crystal structures of human Evectin-2 PH domain for apo and O-phospho-L-serine complexed forms at 1.75 and 1.00 Å resolution, respectively. These structural analyses clearly show that PS-induced conformational change of Evectin-2 PH domain effectively explains the strict phospholipid binding specificity.

  66. Structural basis of the strict phospholipid binding specificity of the pleckstrin homology domain of human evectin-2. International-journal Peer-reviewed

    Seiji Okazaki, Ryuichi Kato, Yasunori Uchida, Tomohiko Taguchi, Hiroyuki Arai, Soichi Wakatsuki

    Acta crystallographica. Section D, Biological crystallography　68　(Pt 2)　117-23　2012/02

    DOI： 10.1107/S0907444911051626 　

    ISSN： 0907-4449

  67. The cytoplasmic tail of heparin-binding EGF-like growth factor regulates bidirectional intracellular trafficking between the plasma membrane and ER. International-journal Peer-reviewed

    Miki Hieda, Michiko Koizumi, Chiduru Higashi, Taro Tachibana, Tomohiko Taguchi, Shigeki Higashiyama

    FEBS open bio　2　(1)　339-44　2012

    DOI： 10.1016/j.fob.2012.09.002 　

    ISSN： 2211-5463

  68. Intracellular phosphatidylserine is essential for retrograde membrane traffic through endosomes. International-journal Peer-reviewed

    Yasunori Uchida, Junya Hasegawa, Daniel Chinnapen, Takao Inoue, Seiji Okazaki, Ryuichi Kato, Soichi Wakatsuki, Ryo Misaki, Masato Koike, Yasuo Uchiyama, Shun-ichiro Iemura, Tohru Natsume, Ryusuke Kuwahara, Takatoshi Nakagawa, Kiyotaka Nishikawa, Kojiro Mukai, Eiji Miyoshi, Naoyuki Taniguchi, David Sheff, Wayne I Lencer, Tomohiko Taguchi, Hiroyuki Arai

    Proceedings of the National Academy of Sciences of the United States of America　108　(38)　15846-51　2011/09/20

    DOI： 10.1073/pnas.1109101108 　

    ISSN： 0027-8424

  69. The recycling endosome protein Rab17 regulates melanocytic filopodia formation and melanosome trafficking. International-journal Peer-reviewed

    Kimberley A Beaumont, Nicholas A Hamilton, Matthew T Moores, Darren L Brown, Norihiko Ohbayashi, Oliver Cairncross, Anthony L Cook, Aaron G Smith, Ryo Misaki, Mitsunori Fukuda, Tomohiko Taguchi, Richard A Sturm, Jennifer L Stow

    Traffic (Copenhagen, Denmark)　12　(5)　627-43　2011/05

    DOI： 10.1111/j.1600-0854.2011.01172.x 　

    ISSN： 1398-9219

    eISSN： 1600-0854

  70. Palmitoylation pilots ras to recycling endosomes. International-journal Peer-reviewed

    Tomohiko Taguchi, Ryo Misaki

    Small GTPases　2　(2)　82-84　2011/03

    Publisher: Taylor and Francis Inc.

    DOI： 10.4161/sgtp.2.2.15245 　

    ISSN： 2154-1256 2154-1248

    eISSN： 2154-1256

  71. Palmitoylated Ras proteins traffic through recycling endosomes to the plasma membrane during exocytosis. International-journal Peer-reviewed

    Ryo Misaki, Miki Morimatsu, Takefumi Uemura, Satoshi Waguri, Eiji Miyoshi, Naoyuki Taniguchi, Michiyuki Matsuda, Tomohiko Taguchi

    The Journal of cell biology　191　(1)　23-9　2010/10/04

    DOI： 10.1083/jcb.200911143 　

    ISSN： 0021-9525

  72. Phosphoinositide 3-kinase δ regulates membrane fission of Golgi carriers for selective cytokine secretion. International-journal Peer-reviewed

    Pei Ching Low, Ryo Misaki, Kate Schroder, Amanda C Stanley, Matthew J Sweet, Rohan D Teasdale, Bart Vanhaesebroeck, Frédéric A Meunier, Tomohiko Taguchi, Jennifer L Stow

    The Journal of cell biology　190　(6)　1053-65　2010/09/20

    DOI： 10.1083/jcb.201001028 　

    ISSN： 0021-9525

  73. Development of magnetic separation system of magnetoliposomes Peer-reviewed

    R. Nakao, Y. Matuo, F. Mishima, T. Taguchi, S. Maenosono, S. Nishijima

    PHYSICA C-SUPERCONDUCTIVITY AND ITS APPLICATIONS　469　(15-20)　1840-1844　2009/08

    DOI： 10.1016/j.physc.2009.05.244 　

    ISSN： 0921-4534

  74. Passage through the Golgi is necessary for Shiga toxin B subunit to reach the endoplasmic reticulum. International-journal Peer-reviewed

    Jenna McKenzie, Ludger Johannes, Tomohiko Taguchi, David Sheff

    The FEBS journal　276　(6)　1581-95　2009/03

    DOI： 10.1111/j.1742-4658.2009.06890.x 　

    ISSN： 1742-464X

  75. Rap2 function requires palmitoylation and recycling endosome localization. International-journal Peer-reviewed

    Yukiko Uechi, Maitsetseg Bayarjargal, Masato Umikawa, Minoru Oshiro, Kimiko Takei, Yoshito Yamashiro, Tsuyoshi Asato, Shogo Endo, Ryo Misaki, Tomohiko Taguchi, Ken-ichi Kariya

    Biochemical and biophysical research communications　378　(4)　732-7　2009/01/23

    DOI： 10.1016/j.bbrc.2008.11.107 　

    ISSN： 0006-291X

  76. Membrane-anchored growth factor, HB-EGF, on the cell surface targeted to the inner nuclear membrane. International-journal Peer-reviewed

    Miki Hieda, Mayumi Isokane, Michiko Koizumi, Chiduru Higashi, Taro Tachibana, Masachika Shudou, Tomohiko Taguchi, Yohki Hieda, Shigeki Higashiyama

    The Journal of cell biology　180　(4)　763-9　2008/02/25

    DOI： 10.1083/jcb.200710022 　

    ISSN： 0021-9525

  77. Retrograde Transport of Glycolipid-Bound Toxins Peer-reviewed

    Ryo Misaki, Tomohiko Taguchi

    Experimental Glycoscience　213-215　2008

    Publisher: Springer Japan

    DOI： 10.1007/978-4-431-77922-3_51 　

  78. Human RME-8 is involved in membrane trafficking through early endosomes. Peer-reviewed

    Akemi Fujibayashi, Tomohiko Taguchi, Ryo Misaki, Masashi Ohtani, Naoshi Dohmae, Koji Takio, Masashi Yamada, Jianguo Gu, Megumi Yamakami, Mitsunori Fukuda, Satoshi Waguri, Yasuo Uchiyama, Tamotsu Yoshimori, Kiyotoshi Sekiguchi

    Cell structure and function　33　(1)　35-50　2008

    DOI： 10.1247/csf.07045 　

    ISSN： 0386-7196

    eISSN： 1347-3700

  79. Spatial segregation of degradation- and recycling-trafficking pathways in COS-1 cells. International-journal Peer-reviewed

    Ryo Misaki, Takatoshi Nakagawa, Mitsunori Fukuda, Naoyuki Taniguchi, Tomohiko Taguchi

    Biochemical and biophysical research communications　360　(3)　580-5　2007/08/31

    DOI： 10.1016/j.bbrc.2007.06.101 　

    ISSN： 0006-291X

  80. Fucosylation of N-Glycans Regulates the Secretion of Hepatic Glycoproteins into Bile Ducts International-journal Peer-reviewed

    Tsutomu Nakagawa, Naofumi Uozumi, Miyako Nakano, Yoko Mizuno-Horikawa, Noriko Okuyama, Tomohiko Taguchi, Jianguo Gu, Akihiro Kondo, Naoyuki Taniguchi, Eiji Miyoshi

    Journal of Biological Chemistry　281　(40)　29797-29806　2006/10

    DOI： 10.1074/jbc.m605697200 　

    ISSN： 0021-9258

  81. A specific detection of GlcNAcbeta1-6Manalpha1 branches in N-linked glycoproteins based on the specificity of N-acetylglucosaminyltransferase VI. International-journal Peer-reviewed

    Tae Watanabe, Hideyuki Ihara, Eiji Miyoshi, Koichi Honke, Naoyuki Taniguchi, Tomohiko Taguchi

    Glycobiology　16　(5)　431-9　2006/05

    DOI： 10.1093/glycob/cwj079 　

    ISSN： 0959-6658

  82. Purification of Rat Liver Golgi Stacks Peer-reviewed

    Yanzhuang Wang, Tomohiko Taguchi, Graham Warren

    Cell Biology　2　33-39　2006

    Publisher: Elsevier

    DOI： 10.1016/B978-012164730-8/50076-9 　 10.1016/b978-012164730-8/50076-9 　

  83. Recycling endosomes can serve as intermediates during transport from the Golgi to the plasma membrane of MDCK cells. International-journal Peer-reviewed

    Agnes Lee Ang, Tomohiko Taguchi, Stephen Francis, Heike Fölsch, Lindsay J Murrells, Marc Pypaert, Graham Warren, Ira Mellman

    The Journal of cell biology　167　(3)　531-43　2004/11/08

    DOI： 10.1083/jcb.200408165 　

    ISSN： 0021-9525

  84. Modulation of the bilayer thickness of exocytic pathway membranes by membrane proteins rather than cholesterol. International-journal Peer-reviewed

    Kakoli Mitra, Iban Ubarretxena-Belandia, Tomohiko Taguchi, Graham Warren, Donald M Engelman

    Proceedings of the National Academy of Sciences of the United States of America　101　(12)　4083-8　2004/03/23

    DOI： 10.1073/pnas.0307332101 　

    ISSN： 0027-8424

  85. Purification and cDNA cloning of UDP-GlcNAc:GlcNAcbeta1-3Galbeta1-4Glc(NAc)-R [GlcNAc to Gal]beta1,6N-acetylglucosaminyltransferase from rat small intestine: a major carrier of dIGnT activity in rat small intestine. International-journal Peer-reviewed

    Hiroaki Korekane, Tomohiko Taguchi, Yoshihiro Sakamoto, Koichi Honke, Naoshi Dohmae, Heidi Salminen, Suvi Toivonen, Jari Helin, Koji Takio, Ossi Renkonen, Naoyuki Taniguchi

    Glycobiology　13　(5)　387-400　2003/05

    DOI： 10.1093/glycob/cwg044 　

    ISSN： 0959-6658

  86. Biochemical sub-fractionation of the mammalian Golgi apparatus. International-journal Peer-reviewed

    Tomohiko Taguchi, Marc Pypaert, Graham Warren

    Traffic (Copenhagen, Denmark)　4　(5)　344-52　2003/05

    DOI： 10.1034/j.1600-0854.2003.00091.x 　

    ISSN： 1398-9219

  87. Partitioning of the matrix fraction of the Golgi apparatus during mitosis in animal cells. International-journal Peer-reviewed

    Joachim Seemann, Marc Pypaert, Tomohiko Taguchi, Jorg Malsam, Graham Warren

    Science (New York, N.Y.)　295　(5556)　848-51　2002/02/01

    DOI： 10.1126/science.1068064 　

    ISSN： 0036-8075

    eISSN： 1095-9203

  88. Molecular cloning and expression of cDNA encoding chicken UDP-N-acetyl-D-glucosamine (GlcNAc): GlcNAc beta 1-6(GlcNAc beta 1-2)-Man alpha 1-R[GlcNAc to Man]beta 1,4N-acetylglucosaminyltransferase VI Peer-reviewed

    Y Sakamoto, T Taguchi, K Honke, H Korekane, H Watanabe, Y Tano, N Dohmae, K Takio, A Horii, N Taniguchi

    JOURNAL OF BIOLOGICAL CHEMISTRY　275　(46)　36029-36034　2000/11

    DOI： 10.1074/jbc.M005860200 　 10.1074/jbc.m005860200 　

    ISSN： 0021-9258

  89. Purification and characterization of UDP-GlcNAc: GlcNac beta 1-6(GlcNAc beta 1-2)Man alpha 1-R [GlcNAc to man]-beta 1, 4-N-acetylglucosaminyltransferase VI from hen oviduct Peer-reviewed

    T Taguchi, T Ogawa, S Inoue, Y Inoue, Y Sakamoto, H Korekane, N Taniguchi

    JOURNAL OF BIOLOGICAL CHEMISTRY　275　(42)　32598-32602　2000/10

    DOI： 10.1074/jbc.M004673200 　 10.1074/jbc.m004673200 　

    ISSN： 0021-9258

  90. Purification and characterization of UDP-GlcNAc : Gal beta 1-4-GlcNAc beta 1-3*Gal beta 1-4Glc (NAc)-R(GlcNAc to *Gal) beta 1, 6N-acetylglucosaminyltransferase from hog small intestine Peer-reviewed

    Y Sakamoto, T Taguchi, Y Tano, T Ogawa, A Leppanen, M Kinnunen, O Aitio, P Parmanne, O Renkonen, N Taniguchi

    JOURNAL OF BIOLOGICAL CHEMISTRY　273　(42)　27625-27632　1998/10

    ISSN： 0021-9258

  91. A method for determination of UDP-GlcNAc: GlcNAc beta 1-6(GlcNAc beta 1-2)Man alpha 1-R [GlcNAc to Man]beta 1-4N-acetylglucosaminyltransferase VI activity using a pyridylaminated tetraantennary oligosaccharide as an acceptor substrate Peer-reviewed

    T Taguchi, T Ogawa, K Kitajima, S Inoue, Y Inoue, Y Ihara, Y Sakamoto, K Nagai, N Taniguchi

    ANALYTICAL BIOCHEMISTRY　255　(1)　155-157　1998/01

    DOI： 10.1006/abio.1997.2465 　

    ISSN： 0003-2697

  92. Occurrence of terminal alpha 2-&gt;8-linked disialylated poly-N-acetyllactosamine chains with Le(X) and I antigenic glycotopes in tetraantennary arms of an N-linked glycoprotein isolated from rainbow trout ovarian fluid Peer-reviewed

    Y Funakoshi, T Taguchi, C Sato, K Kitajima, S Inoue, HR Morris, A Dell, Y Inoue

    GLYCOBIOLOGY　7　(2)　195-205　1997/03

    DOI： 10.1093/glycob/7.2.195 　

    ISSN： 0959-6658

  93. Proton NMR study of triantennary complex type N-linked glycan chains: Assignment of proton chemical shifts of the beta-Man residue in a basic unit of the triantennary glycan chain having a GlcNAc beta 1-&gt;6Man alpha 1-&gt;6Man beta-&gt;sequence Peer-reviewed

    T Taguchi, Y Muto, K Kitajima, S Yokoyama, S Inoue, Y Inoue

    GLYCOBIOLOGY　7　(1)　31-36　1997/02

    DOI： 10.1093/glycob/7.1.31 　

    ISSN： 0959-6658

  94. Activity of UDP-GlcNAc:GlcNAc beta 1-&gt;6(GlcNAc beta 1-&gt;2)Man alpha 1-&gt;R[GlcNAc to Man]beta 1-&gt;4N-acetylglucosaminyltransferase VI (GnT VI) from the ovaries of Oryzias latipes (Medaka fish) Peer-reviewed

    T Taguchi, K Kitajima, S Inoue, Y Inoue, JM Yang, H Schachter, Brockhausen, I

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　230　(3)　533-536　1997/01

    DOI： 10.1006/bbrc.1996.6013 　

    ISSN： 0006-291X

  95. Occurrence and structural analysis of highly sulfated multiantennary N-linked glycan chains derived from a fertilization-associated carbohydrate-rich glycoprotein in unfertilized eggs of Tribolodon hakonensis Peer-reviewed

    T Taguchi, M Iwasaki, Y Muto, K Kitajima, S Inoue, KH Khoo, HR Morris, A Dell, Y Inoue

    EUROPEAN JOURNAL OF BIOCHEMISTRY　238　(2)　357-367　1996/06

    DOI： 10.1111/j.1432-1033.1996.0357z.x 　

    ISSN： 0014-2956

  96. A PRECISE STRUCTURAL-ANALYSIS OF A FERTILIZATION-ASSOCIATED CARBOHYDRATE-RICH GLYCOPEPTIDE ISOLATED FROM THE FERTILIZED-EGGS OF EURYHALINE KILLI FISH (FUNDULUS-HETEROCLITUS) - NOVEL PENTA-ANTENNARY N-GLYCAN CHAINS WITH A BISECTING N-ACETYLGLUCOSAMINYL RESIDUE Peer-reviewed

    T TAGUCHI, K KITAJIMA, Y MUTO, S INOUE, KH KHOO, HR MORRIS, A DELL, RA WALLACE, K SELMAN, Y INOUE

    GLYCOBIOLOGY　5　(6)　611-624　1995/09

    DOI： 10.1093/glycob/5.6.611 　

    ISSN： 0959-6658

    eISSN： 1460-2423

  97. COMPLETE ASSIGNMENTS OF C-13 NMR RESONANCES TO ALL THE CARBON-ATOMS OF THE TRIMANNOSIDO-DI-N-ACETYLCHITOBIOSYL STRUCTURE IN A PENTAANTENNARY DECASACCHARIDE GLYCOPEPTIDE Peer-reviewed

    T TAGUCHI, K KITAJIMA, T NIIMI, Y MUTO, S YOKOYAMA, S INOUE, Y INOUE

    CARBOHYDRATE RESEARCH　275　(1)　185-191　1995/09

    DOI： 10.1016/0008-6215(95)00144-I 　 10.1016/0008-6215(95)00144-i 　

    ISSN： 0008-6215

  98. PROTON NMR-STUDY OF THE TRIMANNOSYL UNIT IN A PENTAANTENNARY N-LINKED DECASACCHARIDE STRUCTURE - COMPLETE ASSIGNMENT OF THE PROTON RESONANCES AND CONFORMATIONAL CHARACTERIZATION Peer-reviewed

    T TAGUCHI, K KITAJIMA, Y MUTO, S YOKOYAMA, S INOUE, Y INOUE

    EUROPEAN JOURNAL OF BIOCHEMISTRY　228　(3)　822-829　1995/03

    DOI： 10.1111/j.1432-1033.1995.0822m.x 　

    ISSN： 0014-2956

  99. IDENTIFICATION AND STRUCTURAL DETERMINATION OF THE KDN-CONTAINING N-LINKED GLYCAN CHAINS CONSISTING OF BIANTENNARY AND TRIANTENNARY COMPLEX-TYPE UNITS OF KDN-GLYCOPROTEIN PREVIOUSLY ISOLATED FROM RAINBOW-TROUT VITELLINE ENVELOPES Peer-reviewed

    T TEZUKA, T TAGUCHI, A KANAMORI, Y MUTO, K KITAJIMA, Y INOUE, S INOUE

    BIOCHEMISTRY　33　(21)　6495-6502　1994/05

    DOI： 10.1021/bi00187a016 　

    ISSN： 0006-2960

  100. STRUCTURAL STUDIES OF A NOVEL TYPE OF PENTAANTENNARY LARGE GLYCAN UNIT IN THE FERTILIZATION-ASSOCIATED CARBOHYDRATE-RICH GLYCOPEPTIDE ISOLATED FROM THE FERTILIZED-EGGS OF ORYZIAS-LATIPES Peer-reviewed

    T TAGUCHI, A SEKO, K KITAJIMA, Y MUTO, S INOUE, KH KHOO, HR MORRIS, A DELL, Y INOUE

    JOURNAL OF BIOLOGICAL CHEMISTRY　269　(12)　8762-8771　1994/03

    ISSN： 0021-9258

    eISSN： 1083-351X

  101. S18.6 Identification and structural determination of the KDN-containing N-linked complex-type glycan chains in a rainbow trout vitelline envelope glycoprotein. The first demonstration of the presence of N-linked KDN-glycan units

    T. Tezuka, T. Taguchi, A. Kanamori, K. Kitajima, Y. Muto, S. Inoue1, Y. Inoue

    Glycoconjugate Journal　10　(4)　328-328　1993/08

    Publisher: Springer Nature

    DOI： 10.1007/bf01210140 　

  102. S9.14 Precise structural determination of unique highly branched multiantennaryN-glycan units present in fish egg hyosophorin

    T. Taguchi, A. Seko, K. Kitajima, S. Inoue, T. Iwamatsu, R. A. Wallace, K. -H. Khoo, H. R. Morris, A. Dell, Y. Inoue

    Glycoconjugate Journal　10　(4)　280-280　1993/08

    Publisher: Springer Nature

    DOI： 10.1007/bf01209986 　

  103. STRUCTURAL STUDIES OF A NOVEL TYPE OF TETRAANTENNARY SIALOGLYCAN UNIT IN A CARBOHYDRATE-RICH GLYCOPEPTIDE ISOLATED FROM THE FERTILIZED-EGGS OF INDIAN MEDAKA FISH, ORYZIAS-MELASTIGMA Peer-reviewed

    T TAGUCHI, A SEKO, K KITAJIMA, S INOUE, T IWAMATSU, KH KHOO, HR MORRIS, A DELL, Y INOUE

    JOURNAL OF BIOLOGICAL CHEMISTRY　268　(4)　2353-2362　1993/02

    ISSN： 0021-9258

    eISSN： 1083-351X

Show all ︎Show first 5

Misc. 84

  1. Mentoring the next generation of cell biologists Invited

    Derek A. Applewhite, Needhi Bhalla, Nina Cabezas-Wallscheid, Neta Erez, Mengfeng Li, Jose M. Polo, Tomohiko Taguchi, Abdou Rachid Thiam, Xiaochen Wang

    Nature Cell Biology　26　(1)　15-18　2024/01/16

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1038/s41556-023-01278-7 　

    ISSN： 1465-7392

    eISSN： 1476-4679

  2. β-arrestinのPIP2新規結合部位の機能解析

    倉本律輝, 生田達也, コドック カリニョ・カーロ・マリオン, 川上耕季, 内田安則, 田口友彦, 柳川正隆, 井上飛鳥

    GPCR研究会プログラム・抄録集　18th　2024

  3. The STING inflammatory signal.

    田口友彦, 朽津芳彦

    月刊臨床免疫・アレルギー科　80　(6)　2023

    ISSN： 1881-1930

  4. LPDS及び7-デヒドロコレステロールレダクターゼ阻害剤(AY9944)同時処理によって,STING経路の活性化は抑制される

    高橋花乃子, 朽津芳彦, 田口友彦

    日本生化学会大会(Web)　96th　2023

  5. アラニンスキャニング変異体解析による自然免疫分子STINGの新規活性制御部位の同定

    湯本瑛亮, 朽津芳彦, 小出頌悟, 向井康治朗, 田口友彦

    日本生化学会大会(Web)　96th　2023

  6. リソソームによる内包化・分解現象の基質:STINGクラスリン被覆小胞クラスター

    進藤瑠璃, 朽津芳彦, 向井康治朗, 和栗聡, 田口友彦

    日本生化学会大会(Web)　96th　2023

  7. 新規レシオ型pHプローブによるリソソーム内腔pHのライブイメージング解析

    栗山卓也, 野本歩夢, 花岡健二郎, 朽津芳彦, 田口友彦

    日本生化学会大会(Web)　96th　2023

  8. PI(3,5)P2によるリソソーム内包化・分解現象の制御

    東海林紬, 朽津芳彦, 篠島あゆみ, 向井康治朗, 田口友彦

    日本生化学会大会(Web)　96th　2023

  9. Autoinflammatory diseases caused by constitutive activation of STING

    進藤瑠璃, 朽津芳彦, 向井康治朗, 田口友彦

    日本免疫不全・自己炎症学会雑誌(Web)　2　(2)　2023

    ISSN： 2435-7693

  10. Novel PIP2 binding site of β arrestin and its function

    CARINO Carlo Marion Codog, 生田達也, 倉本律輝, 川上耕季, 内田安則, 田口友彦, 井上飛鳥

    日本薬学会年会要旨集(Web)　143rd　2023

    ISSN： 0918-9823

  11. リサイクリングエンドソーム局在性ホスファターゼPPP1R12AによるYAPの活性化

    井上智景, 向井康治朗, 松平竜之, 中山淳, 河野望, 青木淳賢, 新井洋由, 内田安則, 田口友彦

    脂質生化学研究　65　2023

    ISSN： 0285-1520

  12. Direct engulfment of STING by lysosome terminates STING signaling

    朽津芳彦, 向井康治朗, 高阿田有希, 篠島あゆみ, 植村武文, 和栗聡, 田口友彦

    日本免疫不全・自己炎症学会雑誌(Web)　1　(2)　2022

    ISSN： 2435-7693

  13. 自然免疫分子STINGのミクロオートファジー分解

    田口友彦, 朽津芳彦, 高阿田有希, 篠島あゆみ, 向井康治朗, 植村武文, 和栗聡

    日本解剖学会総会・全国学術集会講演プログラム・抄録集　127th (CD-ROM)　2022

  14. ホスファチジルイノシトール-4リン酸(PI4P)近傍タンパク質の解析

    倪申い, 向井康治朗, 鈴木健裕, 堂前直, 新井洋由, 田口友彦, 河野望, 青木淳賢

    脂質生化学研究　63　2021

    ISSN： 0285-1520

  15. Endophilin A2による生体膜リン脂質中の多価不飽和脂肪酸の認識

    石野雄己, 齊藤友理, 向井康治朗, 末次志郎, 田口友彦, 新井洋由, 青木淳賢, 青木淳賢

    脂質生化学研究　63　2021

    ISSN： 0285-1520

  16. The molecular mechanism underlying the COPA syndrome

    田口友彦, 向井康治朗

    日本免疫不全・自己炎症学会総会・学術集会プログラム・抄録集　4th　2021

  17. Implications of cholesterol and sphingomyelin in STING phosphorylation by TBK1

    高橋花乃子, 向井康治朗, 田口友彦

    日本細胞生物学会大会(Web)　73rd　2021

  18. Direct engulfment of STING by lysosome terminates STING signaling

    朽津芳彦, 高阿田有希, 篠島あゆみ, 向井康治朗, 田口友彦

    日本細胞生物学会大会(Web)　73rd　2021

  19. 自然免疫分子STINGの小胞体局在性維持機構とその破綻に起因する遺伝性自己炎症性疾患

    向井康治朗, 小川笑満里, 植松黎, 朽津芳彦, 植村武文, 和栗聡, 鈴木健裕, 堂前直, 新井洋由, SHUM Anthony K., 田口友彦

    日本生化学会大会(Web)　93rd　2020

  20. 自然免疫分子STINGのリソソームによる分解機構

    田口友彦, 向井康治朗, 朽津芳彦, 高阿田有希

    日本生化学会大会(Web)　93rd　2020

  21. 自然免疫分子STINGをモデルとしたリソソームへの新規輸送経路の解析

    朽津芳彦, 向井康治朗, 小川笑満里, 新井洋由, 田口友彦, 田口友彦

    次世代を担う若手ファーマ・バイオフォーラム講演要旨集　18th　2019

  22. HER2陽性乳癌治療薬開発標的としての新規Rac1活性化機構の解明

    前川大志, 前川大志, 村上朱里, 村上朱里, 川合克久, 中山淳, 荒木伸一, 仙波憲太郎, 田口友彦, 亀井義明, 高田泰次, 東山繁樹, 東山繁樹

    日本生化学会大会(Web)　92nd　2019

  23. 【細胞高次機能をつかさどるオルガネラコミュニケーション】ゴルジ体およびポストゴルジネットワーク オルガネラプロテオームを解析する新技術

    田口 友彦, 新井 洋由

    生体の科学　69　(6)　568-572　2018/12

    Publisher: (公財)金原一郎記念医学医療振興財団

    ISSN： 0370-9531

  24. 近傍タンパク質ビオチン化タグを利用した初期エンドソームのプロテオミクス解析

    Ni Shenwei, 向井 康治朗, 鈴木 健裕, 堂前 直, 新井 洋由, 田口 友彦

    日本生化学会大会プログラム・講演要旨集　91回　[1T13e-05(1P　2018/09

    Publisher: (公社)日本生化学会

  25. 【オルガネラのバイオロジー最前線】 脂質により特徴付けられるオルガネラ機能

    田口 友彦, 向井 康治朗, 新井 洋由

    細胞　50　(8)　428-431　2018/07

    Publisher: (株)ニュー・サイエンス社

    ISSN： 1346-7557

  26. 【脂質クオリティ 生命機能と健康を支える脂質の多様性】 (第2章)リポクオリティの違いを生み出し識別する機構 細胞内オルガネラ機能のリポクオリティ制御

    向井 康治朗, 新井 洋由, 田口 友彦

    実験医学　36　(10)　1652-1658　2018/06

    Publisher: (株)羊土社

    ISSN： 0288-5514

  27. 【脂質クオリティ 生命機能と健康を支える脂質の多様性】 (第2章)リポクオリティの違いを生み出し識別する機構 細胞内オルガネラ機能のリポクオリティ制御

    向井 康治朗, 新井 洋由, 田口 友彦

    実験医学　36　(10)　1652-1658　2018/06

    Publisher: (株)羊土社

    ISSN： 0288-5514

  28. オルガネラ研究の最前線-細胞応答を司るオルガネラ・ゾーンの発見と創薬への展開- 自然免疫受容体STING活性化におけるゴルジ体膜ゾーンの役割

    新井 洋由, 向井 康治朗, 田口 友彦

    日本薬学会年会要旨集　138年会　(1)　316-316　2018/03

    Publisher: (公社)日本薬学会

    ISSN： 0918-9823

  29. オルガネラ研究の最前線-細胞応答を司るオルガネラ・ゾーンの発見と創薬への展開- 自然免疫受容体STING活性化におけるゴルジ体膜ゾーンの役割

    新井 洋由, 向井 康治朗, 田口 友彦

    日本薬学会年会要旨集　138年会　(1)　316-316　2018/03

    Publisher: (公社)日本薬学会

    ISSN： 0918-9823

  30. Rab23 Peer-reviewed

    Marga Gual-Soler, Tomohiko Taguchi, Jennifer L. Stow, Carol Wicking

    Encyclopedia of Signaling Molecules　4362　2018

    Publisher: Springer International Publishing

    DOI： 10.1007/978-3-319-67199-4_62 　

  31. 高度不飽和脂肪酸欠損細胞の作製とその表現型解析

    石野 雄己, 齊藤 友理, 向井 康治朗, 田口 友彦, 新井 洋由

    生命科学系学会合同年次大会　2017年度　[1LBA-007]　2017/12

    Publisher: 生命科学系学会合同年次大会運営事務局

  32. 脂質膜が活躍する生命現象を探究する 周辺ビオチン化酵素を用いたリン脂質近傍タンパク質の新規同定法

    田口 友彦, 新井 洋由

    生命科学系学会合同年次大会　2017年度　[3AW27-6]　2017/12

    Publisher: 生命科学系学会合同年次大会運営事務局

  33. 細胞毒性を激減させた変異Equinatoxin-IIの創出とスフィンゴミエリンプローブとしての生細胞への応用

    仁木 隆裕, 牧野 麻美, 小林 俊秀, 田口 友彦, 新井 洋由

    生命科学系学会合同年次大会　2017年度　[4LT17-08(3P　2017/12

    Publisher: 生命科学系学会合同年次大会運営事務局

  34. ホスファチジルセリン脱炭酸酵素を用いた細胞質側ホスファチジルセリン消去系の開発

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    生命科学系学会合同年次大会　2017年度　[4P2T19-01(3P　2017/12

    Publisher: 生命科学系学会合同年次大会運営事務局

  35. 細胞質DNA応答分子STINGの遺伝性変異に起因する炎症応答恒常活性化機構の解析

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    生命科学系学会合同年次大会　2017年度　[4P2T24-08(3P　2017/12

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  36. エンドソーム膜のホスファチジルセリンを介したYAPの活性化機構の解明

    松平 竜之, 向井 康治朗, 野口 大心, 長谷川 純矢, 八田 知久, 家村 俊一郎, 夏目 徹, 宮村 憲央, 仁科 博史, 中山 淳, 仙波 憲太郎, 冨田 拓哉, 村田 茂穂, 新井 洋由, 田口 友彦

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  37. 磁性-プラズモンハイブリッドナノ粒子を用いたオートファゴソームの磁気分離

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    日本バイオマテリアル学会大会予稿集　39回　209-209　2017/11

    Publisher: 日本バイオマテリアル学会

  38. 高度不飽和脂肪酸(PUFA)欠損培養細胞の作製

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    脂質生化学研究　59　91-92　2017/06

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    ISSN： 0285-1520

  39. 細胞毒性を軽減した改変Equinatoxin-IIの創出と生細胞への応用

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    脂質生化学研究　59　96-97　2017/06

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    ISSN： 0285-1520

  40. 異物と戦うオルガネラ・細胞内輸送 先天免疫関連分子STINGの膜輸送による活性制御

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    日本細胞生物学会大会講演要旨集　69回　12-12　2017/05

    Publisher: (一社)日本細胞生物学会

  41. 細胞質DNAセンサーSTINGの変異に起因する炎症応答恒常活性化機構の解析

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    日本細胞生物学会大会講演要旨集　69回　45-45　2017/05

    Publisher: (一社)日本細胞生物学会

  42. 高度不飽和脂肪酸欠損培養細胞の作製

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    日本薬学会年会要旨集　137年会　(3)　56-56　2017/03

    Publisher: (公社)日本薬学会

    ISSN： 0918-9823

  43. 細胞質DNAに応答する分子STINGはゴルジ体でパルミトイル化されて活性化する

    向井 康治朗, 田口 友彦, 新井 洋由

    日本生化学会大会プログラム・講演要旨集　89回　[1P-369]　2016/09

    Publisher: (公社)日本生化学会

  44. 細胞質DNAセンサーSTINGの遺伝性変異に起因する炎症応答恒常活性化機構の解析

    秋葉 達也, 植松 黎, 向井 康治朗, 田口 友彦, 新井 洋由

    日本生化学会大会プログラム・講演要旨集　89回　[2T16-01(1P　2016/09

    Publisher: (公社)日本生化学会

  45. 細胞質DNA応答分子STINGの活性化にはゴルジ体の脂質環境が重要である

    菊 史佳, 向井 康治朗, 田口 友彦, 新井 洋由

    日本生化学会大会プログラム・講演要旨集　89回　[2T13-06(2P　2016/09

    Publisher: (公社)日本生化学会

  46. EpsinRはコレラ毒素のリサイクリングエンドソームからゴルジ体への逆行性輸送を制御する

    仁木 隆裕, 松平 竜之, 田口 友彦, 新井 洋由

    日本生化学会大会プログラム・講演要旨集　89回　[2P-221]　2016/09

    Publisher: (公社)日本生化学会

  47. 高度不飽和脂肪酸(PUFA)欠損培養細胞の作製

    齊藤 友理, 石野 雄己, 田口 友彦, 新井 洋由

    日本生化学会大会プログラム・講演要旨集　89回　[3T09-05(2P　2016/09

    Publisher: (公社)日本生化学会

  48. evectin-2はNedd4 family E3 ligasesのRE局在を制御する

    野口 大心, 松平 竜之, 家村 俊一郎, 夏目 徹, 田口 友彦, 新井 洋由

    日本生化学会大会プログラム・講演要旨集　89回　[3T13-06(3P　2016/09

    Publisher: (公社)日本生化学会

  49. リサイクリングエンドソームにおけるホスファチジルセリンフリッパーゼATP8A1のリン酸化による制御

    菅原 小莉, 李 尚憲, 田口 友彦, 新井 洋由

    日本生化学会大会プログラム・講演要旨集　89回　[3T13-07(3P　2016/09

    Publisher: (公社)日本生化学会

  50. リサイクリングエンドソームにおけるホスファチジルセリンフリッパーゼATP8A1のリン酸化による制御

    菅原 小莉, 李 尚憲, 田口 友彦, 新井 洋由

    日本細胞生物学会大会講演要旨集　68回　59-59　2016/05

    Publisher: (一社)日本細胞生物学会

  51. 細胞質DNAに応答する分子STINGはゴルジ体で活性化し炎症応答を誘導する

    向井 康治朗, 田口 友彦, 新井 洋由

    日本細胞生物学会大会講演要旨集　68回　72-72　2016/05

    Publisher: (一社)日本細胞生物学会

  52. 細胞質DNAに応答する分子STINGはゴルジ体で活性化し炎症応答を誘導する

    向井 康治朗, 田口 友彦, 新井 洋由

    脂質生化学研究　58　223-223　2016/05

    Publisher: 日本脂質生化学会

    ISSN： 0285-1520

  53. evectin-2はNedd4 family E3 ligasesのRE局在を制御する

    野口 大心, 松平 竜之, 長谷川 純矢, 家村 俊一郎, 夏目 徹, 田口 友彦, 新井 洋由

    日本細胞生物学会大会講演要旨集　68回　59-59　2016/05

    Publisher: (一社)日本細胞生物学会

  54. コレラ毒素のリサイクリングエンドソームからゴルジ体への輸送はクラスリン、AP-1によって制御される

    仁木 隆裕, 松平 竜之, 田口 友彦, 新井 洋由

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集　88回・38回　[1LBA004]-[1LBA004]　2015/12

    Publisher: (公社)日本生化学会

  55. ホスファチジルセリン(PS)の非対称分布を感知する新規PSプローブ

    菅原 小莉, 李 尚憲, 田口 友彦, 新井 洋由

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集　88回・38回　[1LBA011]-[1LBA011]　2015/12

    Publisher: (公社)日本生化学会

  56. 生体膜ダイナミクスと脂質 細胞質分裂、極性形成、スフィンゴ脂質蓄積症におけるスフィンゴミエリンの不均一な膜分布の可視化

    牧野 麻美, 阿部 充宏, 村手 源英, 稲葉 岳彦, Neval Yilmaz, Hullin-Matsuda Francoise, 岸本 拓磨, 田口 友彦, 新井 洋由, 小林 俊秀

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集　88回・38回　[2W11-p　2015/12

    Publisher: (公社)日本生化学会

  57. リピオドミクスから見えてきた脂質の新機能 基礎から臨床まで 細胞内シグナリングの統合の場としてのオルガネラ膜脂質の機能

    新井 洋由, 田口 友彦

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集　88回・38回　[4S4-4]　2015/12

    Publisher: (公社)日本生化学会

  58. 【脂質疾患学 なぜ"あぶら"の異常が病気を引き起こすのか?その質的量的変化と肥満、がん、不妊症、免疫・皮膚・神経疾患】 (第1章)生体における脂質機能とその最新像 膜リン脂質の非対称性が制御する細胞内膜輸送

    李 尚憲, 田口 友彦, 新井 洋由

    実験医学　33　(15)　2384-2390　2015/09

    Publisher: (株)羊土社

    ISSN： 0288-5514

  59. ホスファチジルセリンフリッパーゼによるリサイクリングエンドソームを介した細胞内膜輸送の制御

    李 尚憲, 内田 安則, 田口 友彦, 新井 洋由

    脂質生化学研究　57　187-188　2015/05

    Publisher: 日本脂質生化学会

    ISSN： 0285-1520

  60. ホスファチジルセリンフリッパーゼは膜切断タンパク質EHD1のリサイクリングエンドソームへのリクルートを介して細胞内輸送を制御する

    李 尚憲, 内田 安則, Wang Jiao, Molday Robert, 田口 友彦, 新井 洋由

    日本薬学会年会要旨集　135年会　(3)　62-62　2015/03

    Publisher: (公社)日本薬学会

    ISSN： 0918-9823

  61. リサイクリングエンドソームに局在するクラスリン分子の機能

    仁木 隆裕, 松平 竜之, 田口 友彦, 新井 洋由

    日本薬学会年会要旨集　135年会　(3)　62-62　2015/03

    Publisher: (公社)日本薬学会

    ISSN： 0918-9823

  62. 生体膜リン脂質分布の不均一性が生み出す生物学 哺乳類の細胞におけるエンドソーム膜のホスファチジルセリンフリッパーゼの機能(Function of phosphatidylserine flippases in endosomal membrane traffic in mammalian cells)

    李 尚憲, 田口 友彦, 新井 洋由

    日本生化学会大会プログラム・講演要旨集　87回　[3S03p-3]　2014/10

    Publisher: (公社)日本生化学会

  63. PIPs代謝によるマクロピノサイトーシスの制御機構の解明

    寺坂 慎平, 前川 大志, 荒木 伸一, 田口 友彦, 新井 洋由

    日本生化学会大会プログラム・講演要旨集　87回　[4T14p-13]　2014/10

    Publisher: (公社)日本生化学会

  64. 極長鎖脂肪酸含有スフィンゴ脂質の生理学的意義の解明

    向井 康治朗, 田口 友彦, 新井 洋由, 小林 俊秀

    日本生化学会大会プログラム・講演要旨集　87回　[2P-059]　2014/10

    Publisher: (公社)日本生化学会

  65. リサイクリングエンドソームに局在するクラスリン分子の同定

    松平 竜之, 田口 友彦, 新井 洋由

    日本生化学会大会プログラム・講演要旨集　87回　[4P-254]　2014/10

    Publisher: (公社)日本生化学会

  66. Sphingomyelin synthase Iはリサイクリングエンドソームのスフィンゴミエリン量を規定する

    谷地 理恵子, 仁木 隆裕, 田口 友彦, 新井 洋由

    脂質生化学研究　56　166-167　2014/05

    Publisher: 日本脂質生化学会

    ISSN： 0285-1520

  67. PI3P phosphataseによるマクロピノサイトーシスの制御

    前川 大志, 田口 友彦, 新井 洋由

    脂質生化学研究　55　53-55　2013/05

    Publisher: 日本脂質生化学会

    ISSN： 0285-1520

  68. evectin-2 PH domainを用いたホスファチジルセリン特異的な新規プローブの開発と応用

    松平 竜之, 内田 安則, 田口 友彦, 新井 洋由

    日本薬学会年会要旨集　133年会　(3)　66-66　2013/03

    Publisher: (公社)日本薬学会

    ISSN： 0918-9823

  69. evectin-2 PH domainを用いたホスファチジルセリン特異的な新規プローブの開発と応用

    松平 竜之, 内田 安則, 田口 友彦, 新井 洋由

    日本生化学会大会プログラム・講演要旨集　85回　2T03-08　2012/12

    Publisher: (公社)日本生化学会

  70. 可視化プローブによる細胞内スフィンゴミエリンの局在解析

    谷地 理恵子, 内田 安則, 小林 俊秀, 田口 友彦, 新井 洋由

    日本生化学会大会プログラム・講演要旨集　85回　2P-095　2012/12

    Publisher: (公社)日本生化学会

  71. 細胞内ホスファチジルセリンはリサイクリングエンドソームにおいて逆行性膜輸送を制御する

    田口 友彦, 新井 洋由

    生化学　84　(6)　500-500　2012/06

    Publisher: (公社)日本生化学会

    ISSN： 0037-1017

  72. エンドソームを介した膜輸送におけるホスファチジルセリンの機能解析

    内田 安則, 李 尚憲, 久下 理, 田口 友彦, 新井 洋由

    脂質生化学研究　54　148-151　2012/05

    Publisher: 日本脂質生化学会

    ISSN： 0285-1520

  73. Equinatoxin-IIを用いた細胞内Sphingomyelinの可視化

    谷地 理恵子, 内田 安則, 小林 俊秀, 田口 友彦, 新井 洋由

    脂質生化学研究　54　159-161　2012/05

    Publisher: 日本脂質生化学会

    ISSN： 0285-1520

  74. 細胞内ホスファチジルセリンは逆行性輸送に必要である

    李 尚憲, 内田 安則, 久下 理, 田口 友彦, 新井 洋由

    日本薬学会年会要旨集　132年会　(3)　108-108　2012/03

    Publisher: (公社)日本薬学会

    ISSN： 0918-9823

  75. evectin-2はホスファチジルセリンと結合し逆行性膜輸送を制御する

    田口 友彦, 内田 安則, 新井 洋由

    日本生化学会大会プログラム・講演要旨集　84回　4S7a-5　2011/09

    Publisher: (公社)日本生化学会

  76. リサイクリングエンドソームのホスファチジルセリンは逆行性膜輸送に必要である

    李 尚憲, 内田 安則, 久下 理, 田口 友彦, 新井 洋由

    日本生化学会大会プログラム・講演要旨集　84回　2T15a-12　2011/09

    Publisher: (公社)日本生化学会

  77. evectin-2はホスファチジルセリン(PS)と結合し、逆行性膜輸送を制御する

    内田 安則, 岡崎 誠司, 加藤 龍一, 若槻 壮市, 田口 友彦, 新井 洋由

    日本生化学会大会プログラム・講演要旨集　84回　2T15a-13　2011/09

    Publisher: (公社)日本生化学会

  78. ヒト由来Evectin-2のPHドメインにおける基質特異性の構造学的洞察

    岡崎 誠司, 内田 安則, 加藤 龍一, 井上 貴雄, 山田 悠介, 田口 友彦, 新井 洋由, 若槻 壮市

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集　83回・33回　2T16-8　2010/12

    Publisher: (公社)日本生化学会

  79. OSBPおよびCOG複合体はゴルジ体コレステロールレベルおよびゴルジ内逆行性輸送を制御する(OSBP and the COG complex regulate Golgi cholesterol level and intra-Golgi retrograde transport)

    西村 多喜, 井上 貴雄, 内田 安則, 山本 章嗣, Lupashin Vladimir, 家村 俊一郎, 夏目 徹, 田口 友彦, 新井 洋由

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集　83回・33回　1P-0503　2010/12

    Publisher: (公社)日本生化学会

  80. Evectin-2はホスファチジルセリンと結合し、リサイクリングエンドソームからゴルジ体への逆行性輸送を制御する

    内田 安則, 井上 貴雄, 長谷川 純矢, 三崎 亮, 岡崎 誠司, 加藤 龍一, 若槻 壮一, 田口 友彦, 新井 洋由

    脂質生化学研究　52　35-38　2010/05

    Publisher: 日本脂質生化学会

    ISSN： 0285-1520

  81. 膜リン脂質トポロジーの生物学 Evectin-2はリサイクリングエンドソームからの逆行性輸送を制御する

    新井 洋由, 内田 安則, 長谷川 純矢, 井上 貴雄, 三崎 亮, 田口 友彦

    日本生化学会大会プログラム・講演要旨集　82回　4S12a-5　2009/09

    Publisher: (公社)日本生化学会

  82. HB-EGFの細胞膜-ER/核膜間メンブレントラフィック経路の解析(The membrane trafficking routes of HB-EGF between the plasma membrane and the ER/nuclear envelope)

    檜枝 美紀, 小泉 美智子, 田口 友彦, 立花 太郎, 松浦 成昭, 東山 繁樹

    日本細胞生物学会大会講演要旨集　61回　224-224　2009/05

    Publisher: (一社)日本細胞生物学会

  83. エンドソーム回収時の逆行性輸送に関与する新規因子evectin-2(Evectin-2, a new factor involved in retrograde traffic at recycling endosome)

    長谷川 純矢, 三崎 亮, 田口 友彦, 新井 洋由

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集　81回・31回　4T11-5　2008/11

    Publisher: (公社)日本生化学会

  84. Integrated functional analysis of disease relation sugar chain and protein.

    TANIGUCHI NAOYUKI, WADA YOSHINAO, SUZUKI TADASHI, TAGUCHI TOMOHIKO, MIYOSHI HIDETOMO, KO KENKOKU, KONDO AKIHIRO, ASAHI MICHIO, IHARA HIDEYUKI, TANABE KAORU, NAKANO MIYAKO

    大阪大学先導的研究オープンセンター年報 平成15年度　104-105　2004

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Books and Other Publications 19

  1. 小児内科54巻4号（2022年4月号）

    田口友彦

    東京医学社　2022/04

  2. 実験医学2022年3月号

    田口

    羊土社　2022/03

  3. The Lipid Vol.32 No.2

    田口友彦、村山圭

    メディカルレビュー社　2021/10

  4. 実験医学 2021年6月号

    田口友彦

    羊土社　2021/05

  5. 生化学 91巻５号

    向井康治朗, 田口友彦

    日本生化学会　2019/10

  6. The Lipid Vol.30 No.4

    田口友彦

    メディカルレビュー社　2019/10

  7. 脂質解析ハンドブック（実験医学別冊）

    田口友彦, 向井康治朗

    羊土社　2019/09

  8. The Lipid Vol.30 No.3

    田口友彦

    メディカルレビュー社　2019/07

  9. 医学のあゆみ Vol.269 No.13

    田口友彦

    医歯薬出版　2019/06

  10. The Lung perspectives Vol.26 No.4

    田口友彦, 向井康治朗

    メディカルレビュー社　2018/12

  11. 実験医学 36巻16号

    田口友彦

    羊土社　2018/10

  12. The Lung perspectives Vol.26 No.3

    田口友彦, 向井康治朗

    メディカルレビュー社　2018/08

  13. 細胞 Vol.50 No.8

    田口友彦, 新井洋由

    ニューサイエンス社　2018/07

  14. 医学のあゆみ Vol.265 No.13

    田口友彦, 向井康治朗

    医歯薬出版　2018/06

  15. 実験医学増刊号 36巻10号

    向井康治朗, 新井洋由, 田口友彦

    羊土社　2018/06

  16. 生体の科学 第69巻 第3号

    田口友彦

    医学書院　2018/05

  17. 臨床免疫・アレルギー科 69巻1号

    小林俊彦, 向井康治朗, 田口友彦, 反町典子

    科学評論社　2018/01

  18. 炎症と免疫 2017年7月号 (Vol.25 No.4)

    向井 康治朗, 田口 友彦

    先端医学社　2017/07

  19. 生物の科学 遺伝（Vol.71 No.2）

    田口友彦

    NTS Inc.　2017/03

Show all Show first 5

Presentations 55

  1. Autoinflammatory diseases caused by constitutive activation of STING

    2023/02/12

  2. A novel mode of autophagy terminates STING signalling Invited

    Tomohiko Taguchi

    2022/12/09

  3. Phenylarsine oxide stimulates STING-mediated innate immune activity

    2022/11/10

  4. 自己炎症性疾患CDC42 C-term病の病態発症の分子機構

    西谷 真彦, 向井 康治朗, 西小森 隆太, 田口 友彦, 笹原 洋二, 八角 高裕

    第74回日本細胞生物学会　2022/06

  5. 発光タンパク質NanoLucを利用したSTING分解のハイスループットスクリーニング

    東海林紬, 朽津芳彦, 篠島あゆみ, 向井康治朗, 田口友彦

    第74回日本細胞生物学会　2022/06

  6. 2xPH (evectin-2) とliquid-disordered相に存在するホスファチジルセリンの結合には 疎水性アミノ酸パッチが必要である

    内田 安則, 田口 友彦

    第74回日本細胞生物学会　2022/06

  7. Molecular mechanism underlying STING acitvation at the Golgi Invited

    2022/06

  8. リソソーム分解を介した自然免疫応答経路STINGシグナルの収束機構

    朽津芳彦, 向井康治朗, 高阿田有希, 篠島あゆみ, 植村武文, 和栗聡, 田口友彦

    第5回日本免疫不全・自己炎症学会学術集会　2022/02/11

  9. 難病COPA異常症の発症分子機構 Invited

    田口友彦, 向井康治朗

    第4回日本免疫不全・自己炎症学会学術集会　2021/02/06

  10. 自然免疫分子STINGのリソソームによる分解機構 Invited

    田口友彦, 向井康治朗, 朽津芳彦, 高阿田有希

    第93 回日本生化学会大会　2020/09/14

  11. cGAMP-dependent multimerization of STING

    2020/06/05

  12. Development of monoclonal antibodies that recognize phosphorylated STING

    2020/06/05

  13. Innate immunity-protein STING recruits downstream kinase TBK at the trans-Golgi network

    2020/06/05

  14. 自然免疫分子STINGの活性化分子機構：ゴルジ体の脂質場の重要性 Invited

    田口友彦

    第92回日本生化学会大会　2019/09/19

  15. The Golgi lipid-domain essential for innate immunity signaling International-presentation Invited

    Tomohiko Taguchi

    1st Japan-Europe Workshop on Glycosphingolipids and Membrane Homeostasis　2019/09/02

  16. Indication of the involvement of a Golgi sphingomyelin-enriched domain in the inntate immunity signalling International-presentation Invited

    Tomohiko Taguchi

    the 25th International Symposium on Glycoconjugates　2019/08/27

  17. 自然免疫分子STINGの活性化を支えるゴルジ体脂質ドメイン Invited

    田口友彦

    第61回日本脂質生化学会　2019/07/05

  18. 自然免疫分子STINGの活性を厳密に制御する細胞内物質輸送 Invited

    田口友彦

    生理研研究会「分泌研究の新展開：その普遍性と多様性」　2019/06/07

  19. Molecular mechanism underlying STING activation and inactivation Invited

    Tomohiko Taguchi

    2018/11/30

  20. 自然免疫分子STINGの活性化メカニズム：ゴルジ体の脂質場の重要性 Invited

    田口友彦

    第11回セラミド研究会 学術集会　2018/10/26

  21. Cell biological analysis of STING activation and inactivation Invited

    Tomohiko Taguchi

    The 13th Drosophilia Research Conference　2018/09/11

  22. The feature of endocytic pathways involved in uptake of microparticles Invited

    Tomohiko Taguchi

    2018/09/07

  23. 自然免疫分子STINGの活性化機構と内在性阻害分子の同定 Invited

    田口友彦

    平成30年度生理学研究所研究会　2018/07/06

  24. 生体内膜リン脂質近傍タンパク質の新規同定法の開発 Invited

    田口友彦

    第60回日本脂質生化学会　2018/06/01

  25. 自然免疫分子STINGの活性化機構 Invited

    田口友彦

    第59回日本生化学会中国・四国支部例会　2018/05/26

  26. 細胞質DNA応答分子STINGの細胞内膜系による活性制御機構 Invited

    田口友彦

    第123回日本解剖学会総会・全国学術集会　2018/03/30

  27. Exocytic trafficking of STING, an innate immunity signaling protein, from the ER International-presentation Invited

    Tomohiko Taguchi

    International Symposium on ER stress, glycosylation, homeostasis and diseases　2018/03/22

  28. 細胞質DNA応答分子STINGの活性化機構 Invited

    田口友彦

    第3回北大・部局横断シンポジウム 研究ネットワーク促進プログラム　2018/01/26

  29. 周辺ビオチン化酵素を用いたリン脂質近傍タンパク質の新規同定法 Invited

    田口友彦

    Consortium of Biological Sciences 2017　2017/12/08

  30. A method to identify proteins adjacent to specific phospholipids in vivo International-presentation Invited

    Tomohiko Taguchi

    International Lipoquality meeting　2017/09/22

  31. 先天免疫関連分子STINGの膜輸送による活性制御 Invited

    田口友彦

    第69回日本細胞生物学会大会　2017/06/13

  32. リン脂質ホスファチジルセリンが制御する細胞内物質輸送 Invited

    田口友彦

    第122回日本解剖学会総会・全国学術集会　2017/03/29

  33. 細胞質DNA応答分子STINGのゴルジ体・エンドソーム系 による活性制御機構 Invited

    田口友彦

    第90回日本薬理学会年会　2017/03/15

  34. 細胞内ホスファチジルセリンの可視化 Invited

    田口友彦

    第4回 JFAS(Japan/Joy of Fatty Acids Secrets/Society)　2017/03/05

  35. PI3P phosphataseによるマクロピノサイトーシスの制御

    前川 大志, 田口 友彦, 新井 洋由

    脂質生化学研究　2013/05

  36. evectin-2 PH domainを用いたホスファチジルセリン特異的な新規プローブの開発と応用

    松平 竜之, 内田 安則, 田口 友彦, 新井 洋由

    日本薬学会年会要旨集　2013/03

  37. 可視化プローブによる細胞内スフィンゴミエリンの局在解析

    谷地 理恵子, 内田 安則, 小林 俊秀, 田口 友彦, 新井 洋由

    日本生化学会大会プログラム・講演要旨集　2012/12

  38. evectin-2 PH domainを用いたホスファチジルセリン特異的な新規プローブの開発と応用

    松平 竜之, 内田 安則, 田口 友彦, 新井 洋由

    日本生化学会大会プログラム・講演要旨集　2012/12

  39. Equinatoxin-IIを用いた細胞内Sphingomyelinの可視化

    谷地 理恵子, 内田 安則, 小林 俊秀, 田口 友彦, 新井 洋由

    脂質生化学研究　2012/05

    More details Close

    Equinatoxin-II(EqtII)は分子量約20kDaのイソギンチャク由来pore-forming toxinである。EqtIIはSphingomyelin(SM)のheadgroupを認識して特異的に結合することから、新規のSMプローブとしての利用が期待される。本研究では、EqtII-GFPを用いた染色によって細胞膜および細胞内膜系のSMを可視化するとともに、既知のSMプローブとして利用されているlyseninとの比較を行った。まずGFP-lyseninとEqtII-GFPでそれぞれCOS-1細胞の細胞膜の染色を行ったところ、GFP-lyseninでは染色がpunctateであるのに対し、EqtII-GFPではより広範囲が染色され、特にleading edgeに強い染色が見られた。また、EqtII-GFPによる染色はGFP-lysenin染色と同様にSM合成阻害剤であるD609処理やSphingomyelinase処理よって著しく減弱したことから、in vivoにおいてもEqtII-GFPがSMに特異的に結合していることが強く示唆された。次に、mKate-lyseninとEqtII-GFPの共染色を行ったところ、mKate-lyseninでは染色されない領域がEqtII-GFPで染色された。また、先にEqtII-GFPで染色した後にmKate-lyseninで染色を行うと、ほとんどmKate-lyseninの染色がみられなくなることから、EqtIIはlyseninで染色されるようなclusteringしたSMも認識して結合していることが示唆された。さらにCOS-1細胞で細胞内膜系のSM染色を行ったところ、GFP-lyseninでは主に後期エンドソーム(LE)に染色が見られた。これに対し、EqtII-GFPではLEの他、生化学的分析からSMが豊富であることが報告されているリサイクリングエンドソーム(RE)にも染色が見られた。これらの結果から、EqtIIはin vivoにおいてlyseninで認識されないような膜環境にあるSMにも結合する可能性が示唆された。(著者抄録)

  40. エンドソームを介した膜輸送におけるホスファチジルセリンの機能解析

    内田 安則, 李 尚憲, 久下 理, 田口 友彦, 新井 洋由

    脂質生化学研究　2012/05

    More details Close

    リサイクリングエンドソーム(Recycling Endosomes、REs)は、形質膜から取り込まれた分子を再び形質膜に戻すリサイクリング経路、形質膜からゴルジ体へと至る逆行性輸送経路に関与している。我々は最近、REsがホスファチジルセリン(PS)に非常に富んだオルガネラであること、evectin-2と呼ばれるタンパク質がPSとの結合を介してREsに局在し、REsを介した逆行性輸送を制御していることを見出した。我々は今回、PSの機能をより直接的に検討するため、PS合成経路に異常を持つ細胞株(PSA-3)を用いて、PS減少下でどのような異常が見られるか検討した。その結果、PS減少下では、(1)逆行性輸送によってゴルジ体へと運ばれるタンパク質(TGN38)が、ゴルジ体から分散すること、(2)TGN38の逆行性輸送が阻害されること、(3)REsを介して形質膜へリサイクルされる分子(トランスフェリン)のリサイクリングが阻害されることを見出した。以上の結果から、PSは逆行性輸送経路のみならず、リサイクリング経路にも必要であり、REsが関与する膜輸送において非常に重要なリン脂質であることが判明した。(著者抄録)

  41. 細胞内ホスファチジルセリンは逆行性輸送に必要である

    李 尚憲, 内田 安則, 久下 理, 田口 友彦, 新井 洋由

    日本薬学会年会要旨集　2012/03

  42. evectin-2はホスファチジルセリン(PS)と結合し、逆行性膜輸送を制御する

    内田 安則, 岡崎 誠司, 加藤 龍一, 若槻 壮市, 田口 友彦, 新井 洋由

    日本生化学会大会プログラム・講演要旨集　2011/09

  43. リサイクリングエンドソームのホスファチジルセリンは逆行性膜輸送に必要である

    李 尚憲, 内田 安則, 久下 理, 田口 友彦, 新井 洋由

    日本生化学会大会プログラム・講演要旨集　2011/09

  44. evectin-2はホスファチジルセリンと結合し逆行性膜輸送を制御する

    田口 友彦, 内田 安則, 新井 洋由

    日本生化学会大会プログラム・講演要旨集　2011/09

  45. OSBPおよびCOG複合体はゴルジ体コレステロールレベルおよびゴルジ内逆行性輸送を制御する(OSBP and the COG complex regulate Golgi cholesterol level and intra-Golgi retrograde transport)

    西村 多喜, 井上 貴雄, 内田 安則, 山本 章嗣, Lupashin Vladimir, 家村 俊一郎, 夏目 徹, 田口 友彦, 新井 洋由

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集　2010/12

  46. ヒト由来Evectin-2のPHドメインにおける基質特異性の構造学的洞察

    岡崎 誠司, 内田 安則, 加藤 龍一, 井上 貴雄, 山田 悠介, 田口 友彦, 新井 洋由, 若槻 壮市

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集　2010/12

  47. Evectin-2はホスファチジルセリンと結合し、リサイクリングエンドソームからゴルジ体への逆行性輸送を制御する

    内田 安則, 井上 貴雄, 長谷川 純矢, 三崎 亮, 岡崎 誠司, 加藤 龍一, 若槻 壮一, 田口 友彦, 新井 洋由

    脂質生化学研究　2010/05

    More details Close

    リサイクリングエンドソーム(RE)は、エンドサイトーシスされたトランスフェリン受容体などの膜タンパク質を再び形質膜へ戻すためのオルガネラとして認識されてきた。我々は最近、形質膜からゴルジ体へと輸送される逆行性輸送について、コレラ毒素(CTX)をプローブとして解析を行い、CTXのゴルジ体への輸送がREを経由することを見出した。しかしながら、REを介した逆行性輸送がどのように制御されているのか、その分子機構は不明である。本研究において我々は、1)PHドメインを有する機能未知分子Evectin-2がPHドメインを介してREに局在すること、2)Evectin-2のPHドメインがホスファチジルセリン(PS)と結合すること、3)REがPSに富んだオルガネラであること、4)PSを介したEvectin-2のRE局在がCTXの逆行性輸送に必要であること、を明らかにした。以上の結果は、これまで解析の進んでいなかったREを介する膜輸送において、REの特徴的な脂質組成(PS)が重要な役割を持つことを分子レベルで示すものである。(著者抄録)

  48. 膜リン脂質トポロジーの生物学 Evectin-2はリサイクリングエンドソームからの逆行性輸送を制御する

    新井 洋由, 内田 安則, 長谷川 純矢, 井上 貴雄, 三崎 亮, 田口 友彦

    日本生化学会大会プログラム・講演要旨集　2009/09

  49. Study of magnetic separation system of magnetolipsomes

    NISHIJIMA Shigehiro, NAKAO Ryousuke, MISHIMA Fumihito, MAENOSONO Shinya, TAGUCHI Tomohiko

    2009/06/11

  50. エンドソーム回収時の逆行性輸送に関与する新規因子evectin-2(Evectin-2, a new factor involved in retrograde traffic at recycling endosome)

    長谷川 純矢, 三崎 亮, 田口 友彦, 新井 洋由

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集　2008/11

  51. A specific detection of GlcNAc ss 1-6Mana1 branches in N-linked glycoproteins from cancer cells based on the specificity of N-acetylglucosaminyltransferase VI

    T. Taguchi, T. Watanabe, H. Ihara, E. Miyoshi, K. Honke, N. Taniguchi

    MOLECULAR & CELLULAR PROTEOMICS　2006/10

  52. Core fucosylation of low density lipoprotein receptor-related protein is required for the function as a internalization for IGFBP3

    SH Lee, M Takahashi, E Miyoshi, A Ekuni, T Taguchi, S Inoue, JG Gu, K Honke, N Taniguchi

    GLYCOBIOLOGY　2005/11

  53. A new method for the detection of GlcNAc beta 1-6Man alpha 1-branches in N-linked glycoproteins based on the specificity of N-acetylglucosaminyltransferase VI

    T Watanabe, H Ihara, K Honke, N Taniguchi, T Taguchi

    GLYCOBIOLOGY　2005/11

  54. Generation and maintenance of epithelial cell polarity

    Olara Mellman, Agnes Lee Ang, Eric Anderson, Steven Francis, Tomohiko Taguchi, Lindsay Murrells, Marc Pypaert, Heike Folsch, Graham Warren

    CELL STRUCTURE AND FUNCTION　2004/05

  55. Partitioning of the enzyme and matrix fractions of the Golgi apparatus during mitosis

    J Seemann, M Pypaert, T Taguchi, G Warren

    MOLECULAR BIOLOGY OF THE CELL　2001/11

Show all Show first 5

Research Projects 12

  1. STINGのリソソームミクロオートファジー分解を制御する分子基盤

    System: 文部科学省 科学研究費補助金 基盤研究（A）

    2024/04 - 2027/03

  2. 細胞内輸送が厳密に制御する自然免疫分子STINGの活性・不活性化の分子機構 Competitive

    田口 友彦

    Offer Organization: 文部科学省

    System: 科学研究費補助金 基盤研究（A）

    2019/04 - 2022/03

  3. 細胞内小器官特異的脂質環境が制御するシグナル伝達とその破綻に起因する疾患の分子機構の解明 Competitive

    田口 友彦

    Offer Organization: 国立研究開発法人日本医療研究開発機構

    System: 革新的先端研究開発支援事業 PRIME「画期的医薬品等の創出をめざす脂質の生理活性と機能の解明」

    2017/10 - 2021/03

  4. リポクオリティが制御する膜マイクロドメインの動態と機能 Competitive

    反町 典子

    Offer Organization: 文部科学省

    System: 科学研究費補助金 新学術領域研究（研究領域提案型）

    2015/06 - 2020/03

  5. Functional analysis of ubiquitin E3 complex scaffold protein,Cullin-3 in breast cancer cells

    Murakami Akari, Maekawa Masashi, Kawai Katsuhisa, Nakayama Jun, Araki Nobukazu, Semba Kentaro, Taguchi Tomohiko, Kamei Yoshiaki, Takada Yasutsugu, Higashiyama Shigeki

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Young Scientists (B)

    Institution: Ehime University

    2017/04 - 2019/03

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    Human breast cancer can be classified by gene expression into four or five subtypes, and the treatment plans are decided based on the subtypes. From this standpoint, it is important to elucidate molecular mechanisms of the determination of breast cancer characteristics, which could lead to the development of novel therapy for breast cancers. In this research proposal, we focused on a ubiquitin E3 scaffold protein, cullin-3 (CUL3), and found that CUL3 is essential for Rac1 activation and cell proliferation specifically in HER2-positive breast cancer cells.

  6. ホスファチジルセリンが制御するリサイクリングエンドソームの機能の解明 Competitive

    田口 友彦

    Offer Organization: 文部科学省

    System: 科学研究費補助金 基盤研究（Ｂ）

    2016/04 - 2019/03

  7. マスターモデュレーターとしてのCUL3システムを標的とした血管新生制御法の開発とがん治療応用 Competitive

    東山 繁樹

    Offer Organization: 国立研究開発法人日本医療研究開発機構

    System: 次世代がん医療創生研究事業

    2016/09 - 2018/03

  8. Molecular basis of angiogenesis regulated by CUL3-dependent membrane trafficking

    Maekawa Masashi, HIGASHIYAMA Shigeki, SAKAUE Tomohisa, TAGUCHI Tomohiko

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Young Scientists (B)

    Institution: Ehime University

    2016/04 - 2018/03

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    Angiogenesis, the formation of new blood vessels, is related to not only development but a variety of diseases like tumor growth/metastasis. Anti-angiogenic drugs are successfully used for cancer therapy. In this study, we identified a novel angiogenic factor, the CUL3/ANKFY1 ubiquitin E3 ligase complex, which determines the cell surface level of integrin, an essential adhesion molecule for angiogenesis. CUL3/ANKFY1 regulated recycling of integrin from endosomes to the plasma membrane in human endothelial cells. The CUL3/ANKFY1 complex might be an attractive protein complex to develop novel anti-angiogenic drugs.

  9. Cell biological studies on membrane lipid distribution and dynamics

    Fujimoto Toyoshi, YAMAMOTO HAYASHI, TAGUCHI TOMOHIKO, TAKATORI SHO

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (A)

    Institution: Nagoya University

    2015/04 - 2018/03

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    Electron microscopic methods to label phosphatidylinositol 3,5-bisphosphate, phosphatidylinositol 3,4-bisphosphate, and phosphatidylserine by quick-freezing and freeze-fracture replica labeling were established and distribution of respective phospholipids were defined at the nanometer scale. Involvement of PML-II in formation of nuclear lipid droplets was found and close relationship between nuclear lipid droplets and PML nuclear body as well as nucleoplasmic reticulum, which is an extension of the nuclear envelope, was shown. Microautophagy of lipid droplets that occurs in budding yeast at stationary phase and in acute nitrogen starvation was shown to proceed in a raft-like membrane domain of the vacuole membrane and Niemann-Pick type C proteins were found to play a critical role in transportation of sterol to generate the membrane domain.

  10. Understanding of autophagy utilizing plasmon imaging and subcellular magnetic separation techniques

    MAENOSONO SHINYA, TAGUCHI TOMOHIKO, MUKAI KOJIRO, TAKAKURA MASAHIRO, WAGURI SATOSHI, MATSUMURA KAZUAKI

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Challenging Exploratory Research

    Institution: Japan Advanced Institute of Science and Technology

    2014/04 - 2017/03

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    We developed ultrasmall magnetic-plasmonic hybrid nanobeads and applied them to the isolation of autophagosomes by applying a magnetic field. The beads were chemically synthesized and comprised an Ag/FeCo/Ag core/shell/shell structure with a mean diameter of 15 nm. The Ag core and the FeCo shell conferred imaging and magnetic separation capabilities, respectively. The nanobeads were transfected into mammalian cells by lipofection. Thirty minutes after lipofection, the nanobeads co-localized with Vps26, and subsequently with LC3. Cell lysates were prepared at the appropriate time points and were subjected to magnetic separation. The separated fraction contained LC3-II, transferrin receptor, and LAMP2, but not LC3-I, suggesting that autophagosomes of endosomal origin had been isolated.

  11. 糖鎖の動態−機能相関への統合的アプローチ Competitive

    木下 タロウ

    Offer Organization: 独立行政法人科学技術振興機構

    System: 戦略的創造研究推進事業

    2004/10 - 2010/03

  12. リサイクリングエンドソームを構成する分子基盤の研究 Competitive

    田口 友彦

    Offer Organization: 文部科学省

    System: 科学研究費補助金 特定領域研究

    Category: 特定領域研究

    Institution: 大阪大学

    2007/04 - 2009/03

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    本年度はリサイクリングエンドソームを通過する膜輸送研究を行う上でのCOS-1細胞(Green Monkdy Kidney Cell)の有用性を確立し、論文発表を行った。物質の分解に関与する細胞小器官(初期エンドソーム、後期エンドソーム、リソソーム)はゴルジ体が形作るリング構造"ゴルジリング"の外側に、物質のリサイクルに関与する細胞小器官(リサイクリングエンドソーム)はゴルジリングの内側に位置することを示したものである。この発見により、標的タンパク質がどの細胞小器官に局在するのか、電子顕微鏡観察に依存せず推定できるようになった。この系を用いて逆行性膜輸送の代表的リガンドであるコレラ毒素の膜輸送経路を解析したところ、トサイクリングエンドソーム通過の必要性が明らかになり(低温処理、A1F処理、Tfn-HRPによるリサイクリングエンドソームの不活化実験など)、更に逆行性膜輸送を制御するタンパク質の同定にもつながった。またリサイクリングエンドソームの必要性はコレラ毒素に制限されるものでなく、HB-EGFといった成長因子sheddingを受けた後、核膜へと逆行輸送される際にも必要であることを示すことができた。 近年の分泌経路におけるリサイクリングエンドソームの役割を考慮すると、リサイクリングエンドソーム上には想像以上に複数の膜輸送経路(分泌経路、リサイクル経路、逆行性膜輸送経路)が交差していることが本研究により明らかとなった。この複雑な膜輸送群をどのように精巧に細胞が制御しているのか、その分子機構を解明していくことが次の課題である。

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Teaching Experience 6

  1. 分子細胞生物学III　東北大学

  2. 生命科学B　東北大学

  3. 細胞生物学　東北大学

  4. 生物学演習Ⅰ　東北大学

  5. 大学院・共通科目C　東北大学大学院

  6. 生命科学A　東北大学

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