A Mechanosensitive RhoA Pathway that Protects Epithelia against Acute Tensile Stress

Dev Cell. 2018 Nov 19;47(4):439-452.e6. doi: 10.1016/j.devcel.2018.09.016. Epub 2018 Oct 11.


Adherens junctions are tensile structures that couple epithelial cells together. Junctional tension can arise from cell-intrinsic application of contractility or from the cell-extrinsic forces of tissue movement. Here, we report a mechanosensitive signaling pathway that activates RhoA at adherens junctions to preserve epithelial integrity in response to acute tensile stress. We identify Myosin VI as the force sensor, whose association with E-cadherin is enhanced when junctional tension is increased by mechanical monolayer stress. Myosin VI promotes recruitment of the heterotrimeric Gα12 protein to E-cadherin, where it signals for p114 RhoGEF to activate RhoA. Despite its potential to stimulate junctional actomyosin and further increase contractility, tension-activated RhoA signaling is necessary to preserve epithelial integrity. This is explained by an increase in tensile strength, especially at the multicellular vertices of junctions, that is due to mDia1-mediated actin assembly.

Keywords: E-cadherin; Myosin VI; RhoA; actomyosin; epithelia; mechanotransduction; tension.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Actins / metabolism
  • Actomyosin / metabolism
  • Adherens Junctions / metabolism*
  • Cadherins / metabolism
  • Epithelial Cells / metabolism*
  • Epithelium / metabolism*
  • Humans
  • Stress, Mechanical*
  • Tensile Strength
  • rhoA GTP-Binding Protein / metabolism*


  • Actins
  • Cadherins
  • Actomyosin
  • rhoA GTP-Binding Protein