2015 年 4 巻 1 号 p. 53-61
Exercise improves the performance of the cardiovascular system, striated muscle, and bones, and reduces obesity. Exercise provides for mechanical forces, which include fluid flow and stretching. These mechanical stimuli alter gene expression, which induces the physiological and pathological response in the organs and cells. However, the molecular mechanism underlying the conversion of mechanical stress into gene expression remains largely unknown. Recently, it has been reported that the mechanical stimuli alter the localization of the transcriptional co-activators MRTF (myocardin-related transcription factor) and YAP (Yes-associated protein)/TAZ (transcriptional co-activator with PDZ-binding motif) through actin remodeling. Since MRTF and YAP/TAZ are retained in the cytoplasm in a monomeric G (globular)-actin-dependent manner, actin polymerization promotes the translocation of MRTF and YAP/TAZ to the nucleus, and regulates the expression of several genes. The Rho family small GTPase member Rho and its effector, Rho-kinase (Rho-associated kinase), are critical regulators of actin remodeling. Rho/Rho-kinase suppresses the severing of actin through LIMK (LIM-kinase) and cofilin phosphorylation, thus enhancing actin polymerization. Mechanical stimuli induce actin polymerization through the Rho/Rho-kinase-LIMK-cofilin pathway. The Rho/Rho-kinase signaling pathway regulates gene expression and cell lineage by controlling the actin-dependent localization of MRTF and YAP/TAZ in response to mechanical stress. In this review, we focus on the molecular mechanism by which Rho/Rho-kinase controls gene expression in response to mechanical stimuli.