YAP regulates cell mechanics by controlling focal adhesion assembly

Abstract

<p>Hippo effectors YAP/TAZ act as on–off mechanosensing switches by sensing modifications in<br />extracellular matrix (ECM) composition and mechanics. The regulation of their activity has<br />been described by a hierarchical model in which elements of Hippo pathway are under the<br />control of focal adhesions (FAs). Here we unveil the molecular mechanism by which cell<br />spreading and RhoA GTPase activity control FA formation through YAP to stabilize the<br />anchorage of the actin cytoskeleton to the cell membrane. This mechanism requires YAP<br />co-transcriptional function and involves the activation of genes encoding for integrins and FA<br />docking proteins. Tuning YAP transcriptional activity leads to the modification of cell<br />mechanics, force development and adhesion strength, and determines cell shape, migration<br />and differentiation. These results provide new insights into the mechanism of YAP<br />mechanosensing activity and qualify this Hippo effector as the key determinant of cell<br />mechanics in response to ECM cues.<br /></p>