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Identification and characterisation of a new phospholipid scramblase

Research Project

Project/Area Number 17K15079
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Structural biochemistry
Research InstitutionOsaka University of Pharmaceutical Sciences

Principal Investigator

Fujii Toshihiro  大阪薬科大学, 薬学部, 助教 (30580104)

Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
KeywordsEros / P2X7 / P2XR7 / ATP / BzATP / scramblase / phosphatidilserine / P2XXR7 / リン脂質スクランブラーゼ / ホスファチジルセリン / P2Xr7 / P2rX7
Outline of Final Research Achievements

We attempted to identify and characterize an unknown phospholipid scramblase molecule that acts on phosphatidylserine (PS) exposure by 3'-O- (4-Benzoylbenzoyl) adenosine 5'-triphosphoric acid (BzATP). We tried a genome-wide CRISPR screen for molecules responsible for BzATP-induced PS exposure with flow cytometry for cell sorting and a next-generation sequence. As a result, we identified a transmembrane protein, essential for reactive oxygen species (Eros), as a necessary component for P2X7 expression on the cell membrane and found that it is an important molecule for PS exposure by BzATP, similar to P2X7.

Academic Significance and Societal Importance of the Research Achievements

ATPを介したPS暴露は、ATP駆動イオンチャネルP2X7を介したCa2+の細胞内の流入が引き金になっていると考えられてきた。しかしながら、Ca2+依存的に働くTMEM16Fが担っており、同時にCa2+非依存的な未知のリン脂質スクランブラーゼがあることは明らかだが、今回同定には至らなかった。この分子は分子機序が不明な細胞のPS暴露が関わっている生理的現象、例えば、筋芽細胞の融合や赤血球成熟に於いて排除された核のクリアランス等の現象を解明できるかもしれない。
また同定されたEros遺伝子は、炎症性サイトカインIL-1βの放出に重要であることが明らかになった。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (1 results)

All 2019

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results)

  • [Journal Article] Functional Expression of the P2X7 ATP Receptor Requires Eros2019

    • Author(s)
      Ryoden Yuta、Fujii Toshihiro、Segawa Katsumori、Nagata Shigekazu
    • Journal Title

      The Journal of Immunology

      Volume: 204 Issue: 3 Pages: 559-568

    • DOI

      10.4049/jimmunol.1900448

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access

URL: 

Published: 2017-04-28   Modified: 2022-01-27  

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