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The PI4-Kinase Complex and Its Role in Plasma Membrane Lipid Homeostasis

Research Project

Project/Area Number 21H02694
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 49010:Pathological biochemistry-related
Research InstitutionNiigata University

Principal Investigator

Nakatsu Fubito  新潟大学, 医歯学系, 准教授 (50360607)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2023: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2022: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2021: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Keywordsplasma membrane / PI4P / シグナル伝達 / 脂質交換輸送 / イノシトールリン脂質 / 細胞膜 / メンブレンコンタクト / プローブ / ホスファチジルセリン / コレステロール
Outline of Research at the Start

PI4K3αはTTC7、EFR3およびFAM126と複合体を形成し、細胞膜においてイノシトールリン脂質PI4Pを合成するPI4キナーゼである。PI4K3α複合体は、PI4P合成を介して細胞膜における脂質輸送・代謝やシグナリングなど様々な生理機能を支えている。本研究では、PI4K3α複合体による細胞膜の脂質恒常性維持の制御と破綻のメカニズムの解明を目指す。

Outline of Final Research Achievements

The lipids that form the plasma membrane fulfill many vital functions, including barrier functions and the regulation of signal transduction. Nonetheless, the details regarding their homeostasis regulation are not well understood. In this study, we aim to clarify these mechanisms, particularly from the standpoint of lipid transport control and signal transduction regulation. By identifying novel lipid transport proteins and developing new probes and biosensors for cell membrane lipids, we have shed light on part of the dynamic regulation mechanism of cell membrane lipids.

Academic Significance and Societal Importance of the Research Achievements

細胞膜は、バリア機能や細胞内外のシグナル受容・伝達など、細胞の生命活動に必須な様々な役割を担う。その主要構成分子である脂質はそれら生理機能の制御の中心的役割を担っており、その制御破綻が種々の疾患に関与することからもその生理的重要性は明らかである。本研究により明らかになった知見は、細胞膜が担う様々な現象のさらなる理解や疾患機序解明、さらには新たな治療薬開発などに結びつく可能性が期待される。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • Research Products

    (15 results)

All 2024 2023 2022 2021

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 5 results) Presentation (7 results) (of which Invited: 3 results) Book (1 results)

  • [Journal Article] Phosphatidylserine turns the gears of phospholipids in B cell lymphoma2024

    • Author(s)
      Nakatsu Fubito、Kawasaki Asami
    • Journal Title

      Journal of Cell Biology

      Volume: 223 Issue: 2

    • DOI

      10.1083/jcb.202401047

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Very-long-chain fatty acids are crucial to neuronal polarity by providing sphingolipids to lipid rafts2023

    • Author(s)
      Honda Atsuko、Nozumi Motohiro、Ito Yasuyuki、Natsume Rie、Kawasaki Asami、Nakatsu Fubito、Abe Manabu、Uchino Haruki、Matsushita Natsuki、Ikeda Kazutaka、Arita Makoto、Sakimura Kenji、Igarashi Michihiro
    • Journal Title

      Cell Reports

      Volume: 42 Issue: 10 Pages: 113195-113195

    • DOI

      10.1016/j.celrep.2023.113195

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chemo- and opto-genetic tools for dissecting the role of membrane contact sites in living cells: recent advances and limitations2023

    • Author(s)
      Fubito Nakatsu, Shinya Tsukiji
    • Journal Title

      Current Opinion in Chemical Biology

      Volume: 73 Pages: 102262-102262

    • DOI

      10.1016/j.cbpa.2022.102262

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 脂質交換輸送ゾーンの制御と機能2023

    • Author(s)
      中津 史
    • Journal Title

      解剖学雑誌

      Volume: 98 (2) Pages: 50-53

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PI4P-driven lipid countertransport at ER–endosome membrane contact sites2022

    • Author(s)
      河嵜 麻実、中津 史
    • Journal Title

      生化学

      Volume: 94 Issue: 4 Pages: 611-615

    • DOI

      10.14952/SEIKAGAKU.2022.940611

    • ISSN
      0037-1017
    • Year and Date
      2022-08-25
    • Related Report
      2022 Annual Research Report
  • [Journal Article] PI4P/PS countertransport by ORP10 at ER–endosome membrane contact sites regulates endosome fission2022

    • Author(s)
      Kawasaki A, Sakai A, Nakanishi H, Hasegawa J, Taguchi T, Sasaki J, Arai H, Sasaki T, Igarashi M, Nakatsu F
    • Journal Title

      J Cell Biol

      Volume: 221 Issue: 1 Pages: 1-19

    • DOI

      10.1083/jcb.202103141

    • URL

      https://pure.teikyo.jp/en/publications/60ec8c88-daf6-48f2-8f3e-12e4cfbad383

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Functions of Oxysterol-Binding Proteins at Membrane Contact Sites and Their Control by Phosphoinositide Metabolism2021

    • Author(s)
      Nakatsu Fubito、Kawasaki Asami
    • Journal Title

      Frontiers in Cell and Developmental Biology

      Volume: 9 Pages: 1-18

    • DOI

      10.3389/fcell.2021.664788

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] メンブレンコンタクトにおける脂質交換輸送が制御するオルガネラダイナミクス2023

    • Author(s)
      中津 史
    • Organizer
      第46回日本分子生物学会年会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 脂質の代謝と交換輸送の接点としての脂質交換輸送ゾーン2023

    • Author(s)
      中津 史
    • Organizer
      第96回日本生化学会大会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Lipid countertransport at membrane contact sites2023

    • Author(s)
      中津 史
    • Organizer
      第75回細胞生物学会大会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 脂質交換輸送ゾーンの制御と機能2023

    • Author(s)
      中津 史
    • Organizer
      第128回日本解剖学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] メンブレンコンタクト操作ツールを用いた脂質交換輸送の機能解明2022

    • Author(s)
      中津 史
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 新規蛍光プローブによる細胞膜ホスファチジルイノシトール 4-リン酸の可視化2022

    • Author(s)
      阿喰 萌香、吉川 優、中津 史、築地 真也
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] イノシトールリン脂質・PI4Pによるメンブレンコンタクトを介した脂質交換輸送制御2021

    • Author(s)
      中津 史
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
  • [Book] Plasma Membrane Shaping2022

    • Author(s)
      Nakatsu F, Kawasaki A
    • Total Pages
      468
    • Publisher
      Academic Press
    • ISBN
      9780323899192
    • Related Report
      2022 Annual Research Report

URL: 

Published: 2021-04-28   Modified: 2025-01-30  

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