After stretching (bottom), relocalization of zyxin to stress fibers helps reinforce them.

Cells exposed to repeated stretching along a unidirectional axis reinforce their actin stress fibers and reorient them to run perpendicular to the direction of strain. The two aspects of the response are regulated independently, report Yoshigi et al. (page 209).Numerous tissues are exposed to repeated mechanical strain and respond by reorganizing their cytoskeletons. Researchers hypothesize that stretch-responsive channels or cell adhesion sites may detect the mechanical force and control downstream changes.

When cells were exposed to mechanical stress, zyxin, a prominent component of focal adhesions, relocalized to actin stress fibers. Zyxin redistribution occurred only when cells were grown on a matrix that allowed integrin engagement, but blocking stretch-activated channels had no effect on zyxin mobilization. Zyxin movement also caused a similar relocalization from focal adhesions to stress fibers of vasodilator-stimulated protein (VASP), which promotes actin polymerization.

In mouse fibroblasts lacking a functional zyxin gene, VASP localization did not shift in response to cyclic stretch, nor did the actin fibers become thickened, as compared with wild-type cells. Significantly, the fibers in the mutant cells were reoriented normally in response to stretch, illustrating that reorientation and reinforcement are mechanistically distinct processes.

It is not yet clear whether zyxin is a mechanosensor itself or is an early protein in the response pathway, but the results do show that focal adhesions are a key factor for detecting and responding to mechanical stress.