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Regulation of protein secretion by an ER cholesterol sensor through organelle contact sites

Research Project

Project/Area Number 20K06562
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 43030:Functional biochemistry-related
Research InstitutionTokyo University of Pharmacy and Life Science

Principal Investigator

WAKANA Yuichi  東京薬科大学, 生命科学部, 助教 (90635187)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsタンパク質分泌 / ゴルジ体 / 小胞体 / コレステロール / オルガネラコンタクト / メンブレントラフィック / トランスゴルジネットワーク / オルガネラ膜接触
Outline of Research at the Start

細胞は、分化・増殖に伴う代謝要求に応じて、どのように細胞内のタンパク質・脂質の輸送をコントロールするのか?私たちは最近、小胞体膜のコレステロールセンサータンパク質であるSCAPが、小胞体とゴルジ体の膜接触場(脂質輸送に働く)を介し、ゴルジ体からの輸送小胞形成とタンパク質分泌を促進することを見出した。本研究は、その分子メカニズムの詳細を解明することを目的とするものであり、その成果として、細胞内物流を司るシグナル分子としてのコレステロールの新たな一面が明らかになることが期待される。

Outline of Final Research Achievements

This study is aimed at understanding the molecular mechanism by which cells regulate protein secretion. Here we established an assay of synchronized transport of influenza virus hemagglutinin (HA) and succeeded in visualizing biogenesis of transport carriers which mediate HA transport from the Golgi complex to the plasma membrane. Our results showed that the HA carrier biogenesis requires cholesterol transport at membrane contact sites (MCSs) between the endoplasmic reticulum (ER) and the Golgi complex, and that the ER cholesterol sensor SCAP induces the HA carrier biogenesis possibly by promoting the cholesterol transport at ER-Golgi MCSs. In this study, we also found the possibility that protein kinase D, a membrane fission factor at the Golgi complex, plays a role in cargo sorting into transport carriers.

Academic Significance and Societal Importance of the Research Achievements

細胞は、インスリンや神経伝達物質、成長因子、コラーゲンなど様々なタンパク質を分泌している。タンパク質分泌は、細胞分化・増殖に重要な役割を果たしているが、その制御機構はこれまでほとんど明らかになっていない。私たちの実験結果は、膜接触部位を介した小胞体からゴルジ体へのコレステロールの輸送が、特定タンパク質のゴルジ体から細胞膜への輸送を促進していることを示唆しており、ゴルジ体の機能制御におけるコレステロールの重要性を示すものである。本研究の成果は、コレステロール代謝異常と関連した様々な疾患の発症・重症化の分子メカニズムの解明につながるものと期待される。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (11 results)

All 2023 2022 2021 2020 Other

All Int'l Joint Research (3 results) Journal Article (5 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (3 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Int'l Joint Research] ICFO-Institut de Ciencies Fotoniques(スペイン)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] ICFO-Institut de Ciencies Fotoniques(スペイン)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] ICFO-Institut de Ciencies Fotoniques(スペイン)

    • Related Report
      2020 Research-status Report
  • [Journal Article] CARTS Formation Assay2023

    • Author(s)
      Yuichi Wakana and Mitsuo Tagaya
    • Journal Title

      Methods in Molecular Biology

      Volume: 2557 Pages: 573-581

    • DOI

      10.1007/978-1-0716-2639-9_34

    • ISBN
      9781071626382, 9781071626399
    • Related Report
      2022 Annual Research Report
  • [Journal Article] Regulation of CARTS biogenesis from the trans-Golgi network through ER–Golgi membrane contact sites2022

    • Author(s)
      若菜 裕一
    • Journal Title

      生化学

      Volume: 94 Issue: 3 Pages: 396-401

    • DOI

      10.14952/SEIKAGAKU.2022.940396

    • ISSN
      0037-1017
    • Year and Date
      2022-06-25
    • Related Report
      2022 Annual Research Report
  • [Journal Article] Sorting of secretory proteins at the trans-Golgi network by TGN462022

    • Author(s)
      Lujan Pablo、Garcia-Cabau Carla、Wakana Yuichi、Rodilla-Ramirez Carmen、Malhotra Vivek、Salvatella Xavier、Garcia-Parajo Maria F.、Campelo Felix
    • Journal Title

      bioRxiv

      Volume: -

    • DOI

      10.1101/2022.04.20.488883

    • Related Report
      2021 Research-status Report
    • Open Access / Int'l Joint Research
  • [Journal Article] The PKD-Dependent Biogenesis of TGN-to-Plasma Membrane Transport Carriers2021

    • Author(s)
      Wakana Yuichi、Campelo Felix
    • Journal Title

      Cells

      Volume: 10 Issue: 7 Pages: 1618-1618

    • DOI

      10.3390/cells10071618

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The ER cholesterol sensor SCAP promotes CARTS biogenesis at ER-Golgi membrane contact sites2021

    • Author(s)
      Wakana Yuichi、Hayashi Kaito、Nemoto Takumi、Watanabe Chiaki、Taoka Masato、Angulo-Capel Jessica、Garcia-Parajo Maria F.、Kumata Hidetoshi、Umemura Tomonari、Inoue Hiroki、Arasaki Kohei、Campelo Felix、Tagaya Mitsuo
    • Journal Title

      Journal of Cell Biology

      Volume: 220 Issue: 1 Pages: 3355-3371

    • DOI

      10.1083/jcb.202002150

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] The ER cholesterol sensor SCAP promotes CARTS biogenesis from the TGN through ER-Golgi membrane contact sites2022

    • Author(s)
      Yuichi Wakana, Felix Campelo, and Mitsuo Tagaya
    • Organizer
      EMBO Workshop, The endoplasmic reticulum: The master regulator of membrane trafficking
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The ER cholesterol sensor SCAP promotes the biogenesis of the TGN-derived transport carriers CARTS at ER-Golgi contact sites2020

    • Author(s)
      Yuichi Wakana、Felix Campelo、Mitsuo Tagaya
    • Organizer
      第72回日本細胞生物学大会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 小胞体膜のコレステロールセンサーであるSCAPは、小胞体-ゴルジ体接触部位においてTGNからのCARTS輸送小胞の形成を促進する2020

    • Author(s)
      若菜裕一、Campelo Felix、多賀谷光男
    • Organizer
      第93回日本生化学会大会
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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