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Mechanisms of actin assembly athte ontractile rings and cell-cell junctions

Research Project

Project/Area Number 18K06223
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 44010:Cell biology-related
Research InstitutionFukushima Medical University

Principal Investigator

Higashi Tomohito  福島県立医科大学, 医学部, 准教授 (70515072)

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: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsフォルミン / 細胞間接着 / 細胞質分裂 / 上皮細胞 / タイトジャンクション / アフリカツメガエル / アクチン細胞骨格 / アドレヘンスジャンクション / Rho / アドヘレンスジャンクション / 分裂収縮環 / ライブイメージング
Outline of Final Research Achievements

Formins are regulated by active Rho GTPases and are involved in the regulation of various cellular processes including cell-cell junction maintenance and contractile ring formation. In this study, I found that two formins Dia1 and Dia2 are localized at tight junctions.But the localization was dispensable for maintenance of cell-cell junction structure and tension generation. Dia3 was localized at contractile rings, but again the localization was dispensable. However, when Dia1 and Dia2 were mislocalized at the contractile ring, we observed increased rate of cytokinesis failure, suggesting that multiple formins under control of the same Rho GTPase function differentially at the junctions and contractile rings and that precise regulation of localization is important for successful cytokinesis.

Academic Significance and Societal Importance of the Research Achievements

細胞接着は日本人が中心的な役割を果たして解明されてきた分野です。本研究は接着部位において細胞骨格を制御する因子について新しい知見を得ることができ細胞接着の研究史に新しい事実を提供できました。また、細胞質分裂が正しく行われることは組織の恒常性の維持のために重要であり、分裂の失敗はゲノムの不安定性を引き起こして発がんの原因となります。多くのがん細胞は細胞間接着に異常をきたすことが知られており、フォルミン分子が接着部位への局在を失ったことによって分裂が失敗するという私たちの発見は発がんのメカニズムの一端を解明につながる可能性があります。

Report

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

    (4 results)

All 2021 2020 2019

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (1 results)

  • [Journal Article] Occludin and tricellulin facilitate formation of anastomosing tight-junction strand network to improve barrier function2021

    • Author(s)
      Saito Akira C.、Higashi Tomohito、Fukazawa Yugo、Otani Tetsuhisa、Tauchi Masashi、Higashi Atsuko Y.、Furuse Mikio、Chiba Hideki
    • Journal Title

      Molecular Biology of the Cell

      Volume: 32 Issue: 8 Pages: 722-738

    • DOI

      10.1091/mbc.e20-07-0464

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular organization, regulation and function of tricellular junctions2020

    • Author(s)
      Higashi Tomohito、Chiba Hideki
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - Biomembranes

      Volume: 1862 Issue: 2 Pages: 183143-183143

    • DOI

      10.1016/j.bbamem.2019.183143

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comprehensive analysis of formin localization in Xenopus epithelial cells.2019

    • Author(s)
      Tomohito Higashi, Rachel E. Stepheson, Ann L. Miller
    • Journal Title

      Molecular Biology of the Cell

      Volume: 30 Issue: 1 Pages: 82-95

    • DOI

      10.1091/mbc.e18-02-0133

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] Dynamic maintenance of tight junction barrier2020

    • Author(s)
      Tomohito Higashi
    • Organizer
      日本分子生物学会
    • Related Report
      2020 Annual Research Report

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

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