Vinculin phosphorylation differentially regulates mechanotransduction at cell-cell and cell-matrix adhesions

J Cell Biol. 2014 Apr 28;205(2):251-63. doi: 10.1083/jcb.201309092. Epub 2014 Apr 21.

Abstract

Cells experience mechanical forces throughout their lifetimes. Vinculin is critical for transmitting these forces, yet how it achieves its distinct functions at cell-cell and cell-matrix adhesions remains unanswered. Here, we show vinculin is phosphorylated at Y822 in cell-cell, but not cell-matrix, adhesions. Phosphorylation at Y822 was elevated when forces were applied to E-cadherin and was required for vinculin to integrate into the cadherin complex. The mutation Y822F ablated these activities and prevented cells from stiffening in response to forces on E-cadherin. In contrast, Y822 phosphorylation was not required for vinculin functions in cell-matrix adhesions, including integrin-induced cell stiffening. Finally, forces applied to E-cadherin activated Abelson (Abl) tyrosine kinase to phosphorylate vinculin; Abl inhibition mimicked the loss of vinculin phosphorylation. These data reveal an unexpected regulatory mechanism in which vinculin Y822 phosphorylation determines whether cadherins transmit force and provides a paradigm for how a shared component of adhesions can produce biologically distinct functions.

Publication types

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

MeSH terms

  • Cadherins / genetics
  • Cadherins / metabolism
  • Cell Adhesion / physiology
  • Cell Communication / physiology*
  • Cell Line, Tumor
  • Extracellular Matrix / genetics
  • Extracellular Matrix / metabolism*
  • Humans
  • Mechanotransduction, Cellular / physiology*
  • Phosphorylation / physiology
  • Proto-Oncogene Proteins c-abl / genetics
  • Proto-Oncogene Proteins c-abl / metabolism
  • Vinculin / genetics
  • Vinculin / metabolism*

Substances

  • Cadherins
  • VCL protein, human
  • Vinculin
  • Proto-Oncogene Proteins c-abl