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Involvement of S1P receptor signaling and exosome release on Parkinson's disease

Research Project

Project/Area Number 18K06657
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
Research InstitutionKobe University

Principal Investigator

Okada Taro  神戸大学, 医学研究科, 准教授 (80304088)

Project Period (FY) 2018-04-01 – 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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsα-シヌクレイン / スフィンゴシン1リン酸受容体 / スフィンゴシン1-リン酸 / エクソソーム / S1P / ガングリオシド / スフィンゴシン1-リン酸受容体 / パーキンソン病 / パルミトイル化 / スフィンゴシン1リン酸
Outline of Final Research Achievements

We already reported that extracellular alpha-synuclein inhibits S1P1 receptor-Gi protein coupling. We also reported S1P1 receptor activity on multivesicular endosomes (MVEs) is critical for the protein sorting into exosomes. In this study we showed the data that extracellular alpha-synuclein actually inhibits S1P1 receptor-Gi protein coupling in MVEs. Furthermore extracellular alpha-synuclein reduced the protein sorting in MVEs and ultimately CD63 level in the exosomes.

Academic Significance and Societal Importance of the Research Achievements

パーキンソン病の患者の神経細胞ではα-シヌクレインの蓄積が報告されている。一方で神経細胞外のα-シヌクレインについてはその意義が不明であった。本研究結果より、細胞外α-シヌクレインによりエキソソームへの積荷タンパク質ソーティングが抑制されることが初めて見出された。神経細胞内のα-シヌクレインやアミロイドタンパク質などはエキソソーム中にソーティングされ、細胞外に放出されることがクリアランスメカニズムとして機能しているという報告もあることから、今回の発見により、細胞外α-シヌクレインにより細胞内α-シヌクレインの蓄積が亢進する可能性が初めて提示された。

Report

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

    (3 results)

All 2020 2019 2018

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

  • [Journal Article] Involvement of Receptor-Mediated S1P Signaling in EGF-Induced Macropinocytosis in COS7 Cells2020

    • Author(s)
      Shubi Ambwene Matovelo, Lifang Zhang, Nesma Nabil Ibrahim Mohamed, Taketoshi Kajimoto, Takeshi Ijuin, Taro Okada, Shun-Ichi Nakamura
    • Journal Title

      Kobe J Med Sci

      Volume: 66

    • NAID

      120006975791

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activation of atypical protein kinase C by sphingosine 1-phosphate revealed by an aPKC-specific activity reporter2019

    • Author(s)
      Kajimoto Taketoshi、Caliman Alisha D.、Tobias Irene S.、Okada Taro、Pilo Caila A.、Van An-Angela N.、Andrew McCammon J.、Nakamura Shun-ichi、Newton Alexandra C.
    • Journal Title

      Science Signaling

      Volume: 12 Issue: 562

    • DOI

      10.1126/scisignal.aat6662

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Extracellular α-synuclein drives sphingosine 1-phosphate receptor subtype 1 out of lipid rafts, leading to impaired inhibitory G protein signaling.2018

    • Author(s)
      Badawy SMM, Okada T, Kajimoto T, Hirase M, Matovelo SA, Nakamura S, Yoshida D, Ijuin T, Nakamura SI.
    • Journal Title

      Journal of Biological Chemistry

      Volume: in press Issue: 21 Pages: 8208-8216

    • DOI

      10.1074/jbc.ra118.001986

    • NAID

      120006554634

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access

URL: 

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

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