A role of microtubule cytoskeleton for mechanosensing

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K20620
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0701:Biology at molecular to cellular levels, and related fields
• Research Institution: Hokkaido University
• Principal Investigator: Nishimura Yukako 北海道大学, 遺伝子病制御研究所, 講師 (90360619)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: メカノバイオロジー / 微小管 / 細胞接着

Outline of Final Research Achievements

Cells have an ability to sense and react mechanical forces. This is called ‘mechanosensing’ which is essential for many biological events such as proliferation, differentiation and cancer metastasis. Focal adhesions are considered one of the ‘sensors’ of mechanisensing, however, how the mechanical cues from the extracellular environment regulate turnover of focal adhesions have not been fully understood. In this project, we have investigated a function of microtubule cytoskeleton, which are thought to physically target and induce adhesion turnover, for mechanosensing. High-resolution time-lapse imaging and its image analysis have revealed that cross-correlations among microtubules, microtubule-binding RhoGEF GEFH1 and its downstream signaling molecules. We are now testing molecular dynamics and their functions of these factors during durotaxis, a cell migration process guided by rigidity gradients from extracellular environment.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

メカノセンシング機構は細胞増殖や分化、細胞移動などのさまざまな生体現象で重要な役割を果たしていることが近年の研究で分かってきた。本研究では細胞内外の環境を操作するための細胞工学技術と高解像度イメージング・画像解析を組み合わせた独自の手法により、これまでに観察されてこなかった新しいシグナル伝達機構を可視化した。本研究で着目した因子群は、多くの癌細胞で過剰に活性化・発現していることが報告されているため、本研究をさらに推進することでメカノセンシングの原理解明だけではなく、メカノセンシングと癌発生との関連性についても新たな知見が得られることが期待できる。