YAP regulates cell mechanics by controlling focal adhesion assembly

Giorgia Nardone, Jorge Oliver- De La Cruz, Jan Vrbsky, Cecilia Martini, Jan Pribyl, Petr Skládal, Martin Pešl, Guido Caluori, Stefania Pagliari, Fabiana Martino, Zuzana Maceckova, Marian Hajduch, Andres Sanz-Garcia, Nicola Maria Pugno, Gorazd Bernard Stokin and Giancarlo Forte ()
Additional contact information
Giorgia Nardone: International Clinical Research Center (ICRC), St Anne’s University Hospital
Jorge Oliver- De La Cruz: International Clinical Research Center (ICRC), St Anne’s University Hospital
Jan Vrbsky: International Clinical Research Center (ICRC), St Anne’s University Hospital
Cecilia Martini: International Clinical Research Center (ICRC), St Anne’s University Hospital
Jan Pribyl: CEITEC MU, Masaryk University
Petr Skládal: CEITEC MU, Masaryk University
Martin Pešl: International Clinical Research Center (ICRC), St Anne’s University Hospital
Guido Caluori: International Clinical Research Center (ICRC), St Anne’s University Hospital
Stefania Pagliari: International Clinical Research Center (ICRC), St Anne’s University Hospital
Fabiana Martino: International Clinical Research Center (ICRC), St Anne’s University Hospital
Zuzana Maceckova: Faculty of Medicine and Dentistry, Institute of Molecular and Translational Medicine, Palacky University Olomouc
Marian Hajduch: Faculty of Medicine and Dentistry, Institute of Molecular and Translational Medicine, Palacky University Olomouc
Andres Sanz-Garcia: Faculty of Pharmacy, University of Helsinki
Nicola Maria Pugno: Laboratory of Bio-inspired and Graphene Nanomechanics, Environmental and Mechanical Engineering, University of Trento
Gorazd Bernard Stokin: International Clinical Research Center (ICRC), St Anne’s University Hospital
Giancarlo Forte: International Clinical Research Center (ICRC), St Anne’s University Hospital

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/ncomms15321

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