Functional analysis of RhoGEF, Solo and intermediate filaments in mechanosignal transduction

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K07335
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cell biology
• Research Institution: Tohoku University
• Principal Investigator: Ohashi Kazumasa 東北大学, 大学院生命科学研究科, 教授 (10312539)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: メカノシグナル / RhoGEF / アクチン骨格 / 中間径フィラメント / 上皮細胞集団 / Rho / Solo

Outline of Final Research Achievements

In this study, we investigated the roles of RhoGEF, Solo, involved in mechanotransduction, on ordering of epithelial cell population. We showed that Solo contributes to align of keratin-8/keratin-18 intermediate filaments along the long axis of epithelial tubules of MDCK cells, which are cultured in 3D collagen gels. We also showed that Solo is required for the generating contractile forces in the lumen and basal regions of the epithelial tubules. Furthermore, we found that knockdown of Solo increases the velocity of collective cell migration of MDCK cells on collagen gel, but has no effect on the velocity of migration of solitary cultured cells. We showed that Solo accumulates in the basal region where contractile force is generated and functions in generating the contractile forces.

Free Research Field

分子細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究は、上皮細胞集団が秩序を形成し管腔構造を形成する過程や集団移動する現象において、その形態や運動を決定する機械的な力を制御する機能蛋白質とその作用機構の一端を明らかにした。これは、上皮組織の恒常性の維持や形態形成の新たな基本的な制御機構の発見であり、疾患発症の新たな原因解明につながることが期待される。また、人為的に細胞集団の形状を操作する技術につながり、再生医療や細胞工学に貢献することが期待される。