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Elucidation of the mechanism underlying the organization and multiple functions of the MAM

Research Project

Project/Area Number 18H02439
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 44010:Cell biology-related
Research InstitutionTokyo University of Pharmacy and Life Science

Principal Investigator

TAGAYA MITSUO  東京薬科大学, 生命科学部, 教授 (30179569)

Co-Investigator(Kenkyū-buntansha) 井上 弘樹  東京薬科大学, 生命科学部, 講師 (10294448)
若菜 裕一  東京薬科大学, 生命科学部, 助教 (90635187)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2019: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
Keywordssyntaxin 17 / 小胞体 / ミトコンドリア / オートファジー / 脂肪滴 / インフラマソーム / MAM / 感染炎症 / ACSL3 / 脂肪適 / マイトファジー / ラフト
Outline of Final Research Achievements

Syntaxin17 (Stx17) is localized in the MAM(mitochondria-associated membrane) and exhibits various functions in response to nutrient situation by binding to different partners. In this study, we obtained the following observations about Stx17. (1) The function of Stx17 is regulated by MAP1B-LC1. (2) Stx17 facilitates lipid droplet formation by regulating the localization of ACSL3, an acyl-CoA synthase involved in lipid droplet formation. The raft structure, which is a membrane microdomain enriched in cholesterol and sphingolipids, is important for the interaction between Stx17 and ACSL3 as well as lipid droplet formation. (3) Stx17 regulates the localization of PGAM5, a protein phosphatase for Drp1, to promote mitochondrial division, and both Stx17 and PGAM5 participate in PINK1-Parkin-mediated mitophagy. (4) Stx17 contributes to the formation of NLRP3 inflammasome

Academic Significance and Societal Importance of the Research Achievements

小胞体とミトコンドリアの接触領域は、様々な細胞現象(例えば、脂質合成、オートファジー、炎症を惹起するインフラマソームの形成)が起こる場所であり、また、パーキンソン病や糖尿病等の病気の発症とも密接に関連する。この接触領域においてStx17は重要な役割を有しており、このタンパク質の機能の解明が進むことによって、細胞機能の理解が大きく進んだ。更なる発展によって関連する疾患の解明につながることが期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (14 results)

All 2021 2020 2019 2018 Other

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 4 results) Presentation (7 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results) Remarks (1 results)

  • [Journal Article] Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)12021

    • Author(s)
      Daniel J Klionsky、Shu Aizawa、Amal Kamal Abdel-Aziz、Sara Abdelfatah、Mahmoud Abdellatif、Asghar Abdoli、Steffen Abel、Hagai Abeliovich、Marie H Abildgaard、Yakubu Princely Abudu、Abraham Acevedo-Arozena、Iannis E Adamopoulos、Khosrow Adeli、Timon E Adolph、Annagrazia Adornetto、Elma Aflaki、Galila Agam et al.
    • Journal Title

      Autophagy

      Volume: 17 Issue: 1 Pages: 1-382

    • DOI

      10.1080/15548627.2020.1797280

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Syntaxin 17 recruits ACSL3 to lipid microdomains in lipid droplet biogenesis.2019

    • Author(s)
      Kimura, H., Arasaki, K., Iitsuka, M., and Tagaya, M.
    • Journal Title

      Contact (Thousand Oaks)

      Volume: 2 Pages: 1-14

    • DOI

      10.1177/2515256419838719

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Syntaxin 17 regulates the localization and function of PGAM5 in mitochondrial division and mitophagy2018

    • Author(s)
      Sugo Masashi、Kimura Hana、Arasaki Kohei、Amemiya Toshiki、Hirota Naohiko、Dohmae Naoshi、Imai Yuzuru、Inoshita Tsuyoshi、Shiba‐Fukushima Kahori、Hattori Nobutaka、Cheng Jinglei、Fujimoto Toyoshi、Wakana Yuichi、Inoue Hiroki、Tagaya Mitsuo
    • Journal Title

      The EMBO Journal

      Volume: 37 Issue: 21

    • DOI

      10.15252/embj.201798899

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Loss of DDHD2, whose mutation causes spastic paraplegia, promotes reactive oxygen species generation and apoptosis2018

    • Author(s)
      Maruyama Tomohiro、Baba Takashi、Maemoto Yuki、Hara-Miyauchi Chikako、Hasegawa-Ogawa Minami、Okano Hirotaka James、Enda Yuki、Matsumoto Kei、Arimitsu Nagisa、Nakao Kazuki、Hamamoto Hiroshi、Sekimizu Kazuhisa、Ohto-Nakanishi Takayo、Nakanishi Hiroki、Tokuyama Takeshi、Yanagi Shigeru、Tagaya Mitsuo、Tani Katsuko
    • Journal Title

      Cell Death & Disease

      Volume: 9 Issue: 8 Pages: 797-811

    • DOI

      10.1038/s41419-018-0815-3

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] MAP1B‐LC1 prevents autophagosome formation by linking syntaxin 17 to microtubules2018

    • Author(s)
      Arasaki Kohei、Nagashima Haruki、Kurosawa Yuri、Kimura Hana、Nishida Naoki、Dohmae Naoshi、Yamamoto Akitsugu、Yanagi Shigeru、Wakana Yuichi、Inoue Hiroki、Tagaya Mitsuo
    • Journal Title

      EMBO reports

      Volume: 19 Issue: 8

    • DOI

      10.15252/embr.201745584

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Syntaxin 17 promotes lipid droplet formation by regulating the distribution of acyl-CoA synthetase 3.2018

    • Author(s)
      Kimura H, Arasaki K, Ohsaki Y, Fujimoto T, Ohtomo T, Yamada J, Tagaya M.
    • Journal Title

      J Lipid Res.

      Volume: in press Issue: 5 Pages: 805-819

    • DOI

      10.1194/jlr.m081679

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] 異種生物Syntaxin 17の局在および機能2020

    • Author(s)
      加藤駿、新崎恒平、多賀谷光男
    • Organizer
      第93回日本生化学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 飢餓時の脂肪滴と隔離膜の形成はsyntaxin17-ACSL3軸によって調節されている2020

    • Author(s)
      岡田直樹、大畑俊貴、新崎恒平、多賀谷光男
    • Organizer
      第93回日本生化学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Syntaxin 17の機能を制御するリン酸化部位の同定2020

    • Author(s)
      新崎恒平、杉沢優太、堂前直、多賀谷光男
    • Organizer
      第93回日本生化学会大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Syntaxin 17と結合タンパク質が織りなす多様な機能2019

    • Author(s)
      新崎恒平、多賀谷光男
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Syntaxin 17はNLRP3インフラマソームの形成に必要である2019

    • Author(s)
      飯塚萌、多賀谷光男、新崎恒平
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] MAMにおける脂質ラフト様構造は脂肪滴形成に重要である2018

    • Author(s)
      木村葉那、新崎恒平、多賀谷光男
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Syntaxin 17 interacts with acyl-CoA synthetase 3 and regulates its translocation from the mitochondria-associated membrane to lipid droplets.2018

    • Author(s)
      Tagaya, M., Kimura, H., Arasaki, K., Ohsaki, Y., Fujimoto, T
    • Organizer
      EMBO Workshop “Membrane Contact Sites in Health and Disease”
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Remarks]

    • URL

      https://www.ls.toyaku.ac.jp/~lmcb-6/

    • Related Report
      2020 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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