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

• MeSH
• buněčná diferenciace genetika   fyziologie   MeSH
• buněčná membrána metabolismus   MeSH
• buněčné linie MeSH
• buněčný převod mechanických signálů genetika   fyziologie   MeSH
• extracelulární matrix metabolismus   MeSH
• fokální adheze genetika   metabolismus   fyziologie   MeSH
• HEK293 buňky MeSH
• jaderné proteiny genetika   metabolismus   MeSH
• lidé MeSH
• mikrofilamenta metabolismus   MeSH
• nádorové buněčné linie MeSH
• pohyb buněk genetika   fyziologie   MeSH
• rhoA protein vázající GTP genetika   metabolismus   MeSH
• stanovení celkové genové exprese MeSH
• transkripční faktory genetika   metabolismus   MeSH
• tvar buňky MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH