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Regulations of ion channels by fluctuation of phospholipids' distribution

Research Project

Project/Area Number 18K19398
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 47:Pharmaceutical sciences and related fields
Research InstitutionKyoto University

Principal Investigator

Hara Yuji  京都大学, 工学研究科, 准教授 (60362456)

Project Period (FY) 2018-06-29 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2018: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Keywordsリン脂質 / リン脂質フリッパーゼ / イオンチャネル / リン脂質配向性 / イオンチャネル制御 / リン脂質非対称分布 / カルシウムイオンチャネル / 生体膜 / リン脂質輸送体
Outline of Final Research Achievements

Phospholipids, the main components of the plasma membrane, are asymmetrically distributed between the inner and the outer leaflets. Previous literatures including our recent finding have shown that the asymmetric distribution of phospholipids governs a variety of cellular processes including membrane biophysics, intracellular signaling, and cell migration. But it is still obscure about the molecular mechanism as to how the changes in phospholipids' distribution contributes to a variety of cellular events. In this project, we have examined the importance of phospholipids' distribution in regulation of membrane proteins. Our results identified one of Ca2+-permeable cation channels regulated by bidirectional transport of phospholipids across the plasma membrane. These results strongly support the importance of the "flip-flop switch" mechanism that changes in the trans-bilayer distribution of lipids regulates the function of membrane proteins including ion channels.

Academic Significance and Societal Importance of the Research Achievements

これまでに多くの研究者が脂質と膜タンパク質の相互作用について従事してきた。しかし脂質は水に溶けない物性、またゲノムに直接コードされない理由から、科学技術が進歩した現在でも解析し難い対象である。そのため脂質環境の微細なゆらぎとイオンチャネル活性調節について深く追求した研究は未だ少ない。本研究にて膜リン脂質によるチャネル制御機構を解明することは、膜脂質とタンパク質の織りなす多様な相互作用を理解し、生体膜に機能的な多様性を賦与する分子機構を解明することにつながる。本申請によりイオンチャネルが関わる細胞応答、さらに個体レベルの恒常性維持機構、病態発症機構等についてさらなる理解深化が期待される。

Report

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

    (9 results)

All 2020 2019 2018

All Presentation (9 results) (of which Int'l Joint Research: 3 results,  Invited: 6 results)

  • [Presentation] リン脂質フリップ・フロップにより制御されるイオンチャネルの同定・解析2020

    • Author(s)
      佐々木映美、原雄二
    • Organizer
      第138回 日本薬理学会近畿部会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Role of mechanosensing machinery in skeletal muscle regeneration2020

    • Author(s)
      Yuji Hara, Kotaro Hirano, Masaki Tsuchiya, Masaki Tsuchiya, Masato Umeda
    • Organizer
      第93回日本薬理学会年会 シンポジウム
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Cell surface flip-flop of phosphatidylserine is critical for PIEZO1-mediated myotube formation2019

    • Author(s)
      Yuji Hara
    • Organizer
      OIST Mini-symposium, The 16th International Membrane Research Forum
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 細胞力覚を基軸とした骨格筋線維再生機構2019

    • Author(s)
      原雄二、平野航太郎、土谷正樹、高林征史、梅田眞郷
    • Organizer
      第92回日本生化学会大会 シンポジウム
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] ell surface flip-flop of phosphatidylserine is critical for PIEZO1-mediated myotube formation2019

    • Author(s)
      Yuji Hara, Masaki Tsuchiya, Masaki Okuda, Kotaro Hirano, Seiji Takabayashi and Masato Umeda
    • Organizer
      OIST Mini-Symposium The 16th International Membrane Research Forum
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 筋再生過程におけるリン脂質輸送体依存的なカルシウム動態の役割2018

    • Author(s)
      原雄二、土谷正樹、平野航太郎、梅田眞郷
    • Organizer
      第4回 日本筋学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] リン脂質フリッパーゼによる筋線維の再生制御機構2018

    • Author(s)
      原雄二、土谷正樹、奥田雅貴、平野航太郎、梅田眞郷
    • Organizer
      第91回 日本生化学会大会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Cell surface flip-flop of phosphatidylserine is critical for PIEZO1-mediated myotube formation2018

    • Author(s)
      Yuji Hara, Masaki Tsuchiya, Kotaro Hirano, Masato Umeda
    • Organizer
      第56回 日本生物物理学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] ell surface flip-flop of phosphatidylserine is critical for PIEZO1-mediated myotube formation2018

    • Author(s)
      Yuji Hara, Masaki Tsuchiya, Masaki Okuda, Kotaro Hirano, Seiji Takabayashi and Masato Umeda
    • Organizer
      The 49th NIPS International Symposium
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited

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Published: 2018-07-25   Modified: 2022-01-27  

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