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Determination of protein composition of the epithelial mechanosensing complex by CRISPR/Cas9-mediated fluorescent protein knock-in

Research Project

Project/Area Number 18K06932
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 48040:Medical biochemistry-related
Research InstitutionThe University of Tokushima

Principal Investigator

KURISU Shusaku  徳島大学, 大学院医歯薬学研究部(医学域), 助教 (40525531)

Project Period (FY) 2018-04-01 – 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 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsメカノバイオロジー / ゲノム編集 / 細胞間接着 / CRISPR/Cas9 / vinculin / ノックイン / catenin / actinin / メカノセンシング / Vinculin / 上皮細胞 / アクチン細胞骨格 / E-cadherin / 上皮
Outline of Final Research Achievements

Epithelial cells are able to sense and respond to external forces. This ability is called as "mechanosensing", which allows epithelial tissues to flexibly change their shape and strength to protect our bodies from external stimuli. The molecular apparatus responsible for epithelial mechanosensation is a large protein complex including E-cadherin. However, it has remained unclear how the protein components that make up the complex cooperate to accomplish mechanosensing functions. In this study, by quantifying several proteins of the epithelial mechanosensing complex, we were able to uncover previously unknown quantitative changes of alpha-actinin and ZO-1 during the course of mechanical responses. This finding contributes to our understanding of the molecular mechanisms of epithelial mechanosensation.

Academic Significance and Societal Importance of the Research Achievements

上皮細胞には外部から加えられた力を感知し応答する能力が備わり、これにより上皮組織は形や強度などを柔軟に変え、外部刺激から我々のからだを守っている。近年この能力の破綻が癌の悪性化を促すことが指摘されており、その分子機構の解明が急がれる。本研究では上皮細胞が力を感知する際のセンサーとなる分子装置の個々の構成タンパク質がどのような量比で構成されるかを明らかにし、力を感知する過程でのそれらの量的変動も捉えることができた。この成果は上皮の力センサーの動作原理の解明という学術的意義が大きいが、将来的には癌の病理の解明や新たな治療法の開発に役立つ可能性がある。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (4 results)

All 2021 2020 2018

All Presentation (4 results)

  • [Presentation] 上皮細胞極性の形成における膜近傍アクチンリングの役割2021

    • Author(s)
      栗栖修作, 米村重信
    • Organizer
      第126回 日本解剖学会総会・全国学術集会、第98回 日本生理学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 上皮細胞間接着のメカノセンシングにおけるアクチン結合タンパク質の量的変化2021

    • Author(s)
      栗栖修作, 米村重信
    • Organizer
      第73回日本細胞生物学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 上皮細胞間接着におけるアクチン結合タンパク質の存在比とその分布2020

    • Author(s)
      栗栖修作、米村重信
    • Organizer
      第72回日本細胞生物学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] Determination of protein composition at epithelial cell-cell junctions by CRISPR/Cas9-mediated fluorescent protein knockin2018

    • Author(s)
      Shusaku Kurisu, and Shigenobu Yonemura.
    • Organizer
      Joint Annual Meeting of JSDB 51st and JSCB 70th
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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