YAP regulates cell mechanics by controlling focal adhesion assembly

Nature Communications
Giorgia NardoneGiancarlo Forte

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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Datasets Mentioned

BETA
E-MTAB-5217

Methods Mentioned

BETA
GTPase
PCR
atomic force microscopy
immunoprecipitation
ChIP-Seq
transfection
AFM
confocal microscopy
Assay
ChIP

Software Mentioned

GraphPad Prism
ChIPSeek
FASTQC
HOMER
Bio
JPK
ChIP
ImageJ
Rad Image Lab
Matlab

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