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Mechanical forces facilitate actin polymerization at focal adhesions in a zyxin-dependent manner

Cell Mechanosensing Project, ICORP/SORST, Japan Science and Technology Agency, 65 Tsurumai, Showa-ku, Nagoya, Aichi 466-8550, Japan.
Journal of Cell Science (Impact Factor: 5.33). 10/2008; 121(Pt 17):2795-804. DOI: 10.1242/jcs.030320
Source: PubMed

ABSTRACT We examined the effects of mechanical forces on actin polymerization at focal adhesions (FAs). Actin polymerization at FAs was assessed by introducing fluorescence-labeled actin molecules into permeabilized fibroblasts cultured on fibronectin. When cell contractility was inhibited by the myosin-II inhibitor blebbistatin, actin polymerization at FAs was diminished, whereas alpha(5)beta(1) integrin remained accumulated at FAs. This suggests that actin polymerization at FAs depends on mechanical forces. To examine the action of mechanical forces more directly, the blebbistatin-treated cells were subjected to a sustained uniaxial stretch, which induced actin polymerization at FAs. These results demonstrate the novel role of mechanical forces in inducing 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 zyxin-rich FAs. Accumulation of zyxin at FAs was diminished by blebbistatin, whereas uniaxial stretching of the cells induced zyxin accumulation. Displacing endogenous zyxin from FAs by expressing the FA-targeting region of zyxin decreased the force-induced actin polymerization at FAs. These results suggest that zyxin is involved in mechanical-force-dependent facilitation of actin polymerization at FAs.

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    • "Integrins can either be part of focal complexes located in the posterior region of a lamellipodia or in focal adhesions (FAs) [2], which are formed upon the suspension of advancement or retraction of the cell's leading edge. Here, ß3 integrin particularly in conjunction with zyxin has been reported during the transition from focal complexes to definitive FAs, also called mature or late stage FAs ([3] [4] [5], for review see [6] [7]). With respect to FAs, integrins involved in their formation belong to the ß3 and/or ß1 families [1], the latter also constituting fibrillar adhesions in 2D cell cultures [8]. "
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