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Mechanism of Exosome Production by Heterotrimeric G Protein Signaling

Research Project

Project/Area Number 19K07043
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 InstitutionGifu University

Principal Investigator

Ueda Hiroshi  岐阜大学, 工学部, 教授 (50253779)

Co-Investigator(Kenkyū-buntansha) 赤尾 幸博  岐阜大学, 大学院連合創薬医療情報研究科, 特任教授 (00222505)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
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)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsGPCR / エクソソーム / PKA / CD81 / 細胞外小胞 / small GTPase / Gタンパク質
Outline of Research at the Start

がん悪性化に関与すると考えられているエクソソームの産生機構を解明することは、現在の細胞生物学分野において重要なトピックである。申請者らは、エクソソーム産生には、エンドサイトーシスにより形成される多胞性エンドソーム(MVE)の関与が重要であり、三量体G蛋白質共役型受容体(GPCR)を含む各種レセプターからのシグナルが深く関与していることに着目した。そこで、エクソソーム産生に影響を与えることが予想されるGPCRシグナルを手掛かりにして得たいくつかの候補分子の中から、エクソソーム産生制御の中心的役割を担う分子を同定することを目指す。同定された分子が新規創薬ターゲットになると期待される。

Outline of Final Research Achievements

In recent years, it has been reported that extracellular signaling by exosomes containing RNA and proteins is employed in various cells to induce various cellular responses. It is also known that exosomes are highly relevant to pathological conditions such as cancer, and elucidation of the exosome production mechanism may lead to the treatment of these pathological conditions. In this study, we investigated the mechanism of exosome production by GPCR stimulation and attempted to identify molecules involved in promoting and inhibiting exosome production. We found that there is a regulatory mechanism of exosome production by Gs signaling that is independent of cAMP-dependent protein kinases.

Academic Significance and Societal Importance of the Research Achievements

本研究では、エクソソーム産生機構の一つとして、三量体Gタンパク質共役型受容体(GPCR)刺激の中でも、Gsシグナルに関わる経路について検討した研究であり、過去、そのような研究報告はほとんどない。さらに、エクソソームの放出機構について、促進と抑制に関わる分子の同定を試みている点でも、これらの結果を利用し、今後、がんに関わる治療薬開発や、エクソソームを利用した薬物送達にも応用できると考えられる。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (12 results)

All 2022 2021 2020 2019

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 3 results) Presentation (5 results)

  • [Journal Article] Impaired Function of PLEKHG2, a Rho-Guanine Nucleotide-Exchange Factor, Disrupts Corticogenesis in Neurodevelopmental Phenotypes.2022

    • Author(s)
      Nishikawa M, Ito H, Tabata H, Ueda H, Nagata KI.
    • Journal Title

      Cells

      Volume: 16 Issue: 4 Pages: 696-696

    • DOI

      10.3390/cells11040696

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Rho guanine nucleotide exchange factor PLEKHG1 is activated by interaction with and phosphorylation by Src family kinase member FYN.2022

    • Author(s)
      Nakano S, Nishikawa M, Kobayashi T, Harlin EW, Ito T, Sato K, Sugiyama T, Yamakawa H, Nagase T, Ueda H.
    • Journal Title

      J Biol Chem

      Volume: 298 Issue: 2 Pages: 101579-101579

    • DOI

      10.1016/j.jbc.2022.101579

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Petasin potently inhibits mitochondrial complex I-based metabolism that supports tumor growth and metastasis.2021

    • Author(s)
      Heishima K, Sugito N, Soga T, Nishikawa M, Ito Y, Honda R, Kuranaga Y, Sakai H, Ito R, Nakagawa T, Ueda H, Akao Y
    • Journal Title

      J Clin Invest

      Volume: 131 Issue: 17

    • DOI

      10.1172/jci139933

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Specific inhibition of oncogenic RAS using cell-permeable RAS-binding domains2021

    • Author(s)
      Nomura, T.K., Heishima, K., Sugito, N., Sugawara, R., Ueda, H., Akao, Y. and Honda, R.
    • Journal Title

      Cell Chemical Biology

      Volume: - Issue: 11 Pages: 1581-1589.e6

    • DOI

      10.1016/j.chembiol.2021.04.013

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] DBS is activated by EPHB2/SRC signaling-mediated tyrosine phosphorylation in HEK293 cells2019

    • Author(s)
      Nakano Shun、Nishikawa Masashi、Asaoka Rina、Ishikawa Natsuko、Ohwaki Chisato、Sato Katsuya、Nagaoka Hitoshi、Yamakawa Hisashi、Nagase Takahiro、Ueda Hiroshi
    • Journal Title

      Molecular and Cellular Biochemistry

      Volume: 459 Issue: 1-2 Pages: 83-93

    • DOI

      10.1007/s11010-019-03552-5

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Structural and functional characterization of fast-cycling RhoF GTPase.2019

    • Author(s)
      Sugawara R, Ueda H, Honda R.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 513(2) Issue: 2 Pages: 522-527

    • DOI

      10.1016/j.bbrc.2019.04.018

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] The interaction between PLEKHG2 and ABL1 suppresses cell growth via the NF-κB signaling pathway in HEK293 cells2019

    • Author(s)
      Nishikawa Masashi、Nakano Shun、Nakao Hiromu、Sato Katsuya、Sugiyama Tsuyoshi、Akao Yukihiro、Nagaoka Hitoshi、Yamakawa Hisashi、Nagase Takahiro、Ueda Hiroshi
    • Journal Title

      Cellular Signalling

      Volume: 61 Pages: 93-107

    • DOI

      10.1016/j.cellsig.2019.04.016

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] アダプタータンパク質NCK2によるSH3ドメインを介したRho活性化因子PLEKHG1の活性制御2021

    • Author(s)
      井藤 拓哉、後藤 未沙紀、中野 駿、西川 将司、山川 央、長瀬 隆弘、上田 浩
    • Organizer
      日本薬学会 第141年会
    • Related Report
      2020 Research-status Report
  • [Presentation] 非受容体型チロシンキナーゼ FYNによる Rho活性化因子 PLEKHG1の活性制御2020

    • Author(s)
      中野 駿、 西川 将司、小林 知世、杉山 剛志、山川 央、長瀬 隆弘、上田 浩
    • Organizer
      日本生化学会 第93回日本生化学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] 嗅覚受容体における新規短鎖脂肪酸受容体の同定2019

    • Author(s)
      八橋茉利奈、吉田泰徳、今枝孝夫、西川将司、中野駿、喜多村徳昭、池田将、榊原清美、本山ユミ、長瀬隆弘、上田浩
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] 三量体G蛋白質GiシグナルによるRho活性化因子PLEKHG1の活性制御2019

    • Author(s)
      西川将司、中野駿、山川央、長瀬隆弘、上田浩
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] SH3ドメインを介したアダプター蛋白質NCK2によるRho活性化因子PLEKHG1の機能制御2019

    • Author(s)
      後藤美沙紀、西川将司、中野駿、山川央、長瀬隆弘、上田浩
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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