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

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K06932
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48040:Medical biochemistry-related
• Research Institution: The 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
• 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

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.

Free Research Field

細胞生物学

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。