Activation mechanisms and functions of Solo in mechanoresponses

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K14469
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Functional biochemistry
• Research Institution: Tohoku University
• Principal Investigator: Mizuno Kensaku 東北大学, 生命科学研究科, 教授 (70128396)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 細胞骨格 / メカニカルストレス / アクチン / Rho / Rho-GEF

Outline of Final Research Achievements

Mechanical force-induced cytoskeletal reorganization is essential for cell and tissue remodeling and homeostasis. Solo (ARHGEF40) is a RhoA-targeting guanine nucleotide exchange factor (GEF) involved in cyclic stretch-induced endothelial cell reorientation. In this study, we showed that Solo binds to keratin-8/18 (K8/K18) intermediate filaments through multiple sites. Knockdown of Solo suppressed stress fiber formation and led to disorganized keratin networks, indicating that the Solo serves to precisely organize keratin networks as well as to promote stress fibers. Knockdown of Solo or K18 suppressed tensile force-induced RhoA activation and stress fiber reinforcement. These results suggest that Solo and K8/K18 filaments play crucial roles in tensile force-induced RhoA activation and consequent actin cytoskeletal reinforcement. We also provided evidence that Solo plays roles in collective cell migration and tubule formation.

Free Research Field

細胞生物学