YAP regulates cell mechanics by controlling focal adhesion assembly

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Cell Cycle Proteins
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology
  • Cell Line
  • Cell Line, Tumor
  • Cell Membrane / metabolism
  • Cell Movement / genetics
  • Cell Movement / physiology
  • Cell Shape
  • Extracellular Matrix / metabolism
  • Focal Adhesions / genetics
  • Focal Adhesions / metabolism
  • Focal Adhesions / physiology*
  • Gene Expression Profiling
  • HEK293 Cells
  • Humans
  • Mechanotransduction, Cellular / genetics
  • Mechanotransduction, Cellular / physiology*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • rhoA GTP-Binding Protein / genetics
  • rhoA GTP-Binding Protein / metabolism

Substances

  • Cell Cycle Proteins
  • Nuclear Proteins
  • Transcription Factors
  • YY1AP1 protein, human
  • rhoA GTP-Binding Protein