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Nat Commun. 2017 May 15;8:15321. doi: 10.1038/ncomms15321.

YAP regulates cell mechanics by controlling focal adhesion assembly.

Author information

1
International Clinical Research Center (ICRC), St Anne's University Hospital, CZ-65691 Brno, Czech Republic.
2
CEITEC MU, Masaryk University, CZ-65691 Brno, Czech Republic.
3
Faculty of Medicine, Department of Biology, Masaryk University, CZ-62500 Brno, Czech Republic.
4
Faculty of Medicine and Dentistry, Institute of Molecular and Translational Medicine, Palacky University Olomouc, Hněvotínská 1333/5, CZ-77515 Olomouc, Czech Republic.
5
Faculty of Pharmacy, Division of Pharmaceutical Biosciences, University of Helsinki, Viikinkaari 5 E, FI-00014 Helsinki, Finland.
6
Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-Cho, Shinjuku-Ku, Tokyo JP-162-8666, Japan.
7
Laboratory of Bio-inspired and Graphene Nanomechanics, Department of Civil, Environmental and Mechanical Engineering, University of Trento, I-38123 Trento, Italy.
8
Ket-Lab, Italian Space Agency, Via del Politecnico snc, 00133 Rome, Italy.
9
School of Engineering and Materials Science, Queen Mary University of London, Mile End Road, UK-E1 4NS London, UK.
10
Department of Biomaterials Science, Institute of Dentistry, University of Turku, FI-20014 Turku, Finland.

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.

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