Abstract
It has been established that intra- and extracellular mechanical environments affect the development of focal adhesions (FAs), however, little is known about its molecular mechanisms. FA is a site where actin polymerizes, and the assembly of produced F-actin at FAs is thought to be crucial for the development of FAs. Therefore, we examined the effects of mechanical forces on actin polymerization at FAs. When cell contractility was inhibited by the myosin II inhibitor blebbistatin, actin polymerization at FAs was diminished. By contrast, when blebbistatin-treated cells were subjected to a sustained uniaxial stretch, the actin polymerization was restored. These results demonstrate the novel role of mechanical forces in actin polymerization at FAs. To reveal the molecular mechanism underlying the force-induced actin polymerization at FAs, we examined the distribution of zyxin, a postulated actin-regulatory protein. Actin polymerizing activity was strong at FAs with large amounts of zyxin. Accumulation of zyxin at FAs was diminished by blebbistatin, but was restored by a uniaxial stretch. When endogenous zyxin was displaced from FAs by expressing the FA-targeting region of zyxin, the force-induced actin polymerization at FAs was decreased. These results provide direct evidence that zyxin is involved in the mechanical force-dependent facilitation of actin polymerization at FAs. [J Physiol Sci. 2008;58 Suppl:S203]
