Rac1 functions as a reversible tension modulator to stabilize VE-cadherin trans-interaction

J Cell Biol. 2015 Jan 5;208(1):23-32. doi: 10.1083/jcb.201409108.

Abstract

The role of the RhoGTPase Rac1 in stabilizing mature endothelial adherens junctions (AJs) is not well understood. In this paper, using a photoactivatable probe to control Rac1 activity at AJs, we addressed the relationship between Rac1 and the dynamics of vascular endothelial cadherin (VE-cadherin). We demonstrated that Rac1 activation reduced the rate of VE-cadherin dissociation, leading to increased density of VE-cadherin at AJs. This response was coupled to a reduction in actomyosin-dependent tension across VE-cadherin adhesion sites. We observed that inhibiting myosin II directly or through photo-release of the caged Rho kinase inhibitor also reduced the rate of VE-cadherin dissociation. Thus, Rac1 functions by stabilizing VE-cadherin trans-dimers in mature AJs by counteracting the actomyosin tension. The results suggest a new model of VE-cadherin adhesive interaction mediated by Rac1-induced reduction of mechanical tension at AJs, resulting in the stabilization of VE-cadherin adhesions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Webcast

MeSH terms

  • Actomyosin / metabolism
  • Adherens Junctions / drug effects
  • Adherens Junctions / enzymology*
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Cell Adhesion
  • Cells, Cultured
  • Endothelial Cells / drug effects
  • Endothelial Cells / enzymology*
  • Enzyme Activation
  • Humans
  • Kinetics
  • Microscopy, Fluorescence
  • Microscopy, Video
  • Models, Biological
  • Myosin Type II / metabolism
  • Protein Binding
  • Protein Kinase Inhibitors / pharmacology
  • Protein Multimerization
  • Protein Stability
  • Time-Lapse Imaging
  • Transfection
  • rac1 GTP-Binding Protein / genetics
  • rac1 GTP-Binding Protein / metabolism*
  • rho-Associated Kinases / antagonists & inhibitors
  • rho-Associated Kinases / metabolism

Substances

  • Antigens, CD
  • Cadherins
  • Protein Kinase Inhibitors
  • RAC1 protein, human
  • cadherin 5
  • Actomyosin
  • rho-Associated Kinases
  • Myosin Type II
  • rac1 GTP-Binding Protein