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YAP regulates cell mechanics by controlling focaladhesion assembly

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NARDONE Giorgia CRUZ Jorge Oliver-De La VRBSKÝ Jan MARTINI Cecilia PŘIBYL Jan SKLÁDAL Petr PEŠL Martin CALUORI Guido PAGLIARI Stefania MARTINO Fabiana MACECKOVA Zuzana HAJDÚCH Marian SANZ-GARCIA Andres PUGNO Nicola Maria STOKIN Gorazd Bernard FORTE Giancarlo

Druh Článek v odborném periodiku
Časopis / Zdroj NATURE COMMUNICATIONS
Fakulta / Pracoviště MU

Lékařská fakulta

Citace
WWW https://www.nature.com/articles/ncomms15321
Doi http://dx.doi.org/10.1038/ncomms15321
Obor Genetika a molekulární biologie
Klíčová slova Hippo effectors YAP/TAZ; mechanosensing; extracellular matrix; focal adhesions; RhoA GTPase activity; actin cytoskeleton
Popis 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.
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