Fibronectin rigidity response through Fyn and p130Cas recruitment to the leading edge

Mol Biol Cell. 2006 Jun;17(6):2684-95. doi: 10.1091/mbc.e05-12-1161. Epub 2006 Apr 5.

Abstract

Cell motility on extracellular matrices critically depends on matrix rigidity, which affects cell adhesion and formation of focal contacts. Receptor-like protein tyrosine phosphatase alpha (RPTPalpha) and the alphavbeta3 integrin form a rigidity-responsive complex at the leading edge. Here we show that the rigidity response through increased spreading and growth correlates with leading edge recruitment of Fyn, but not endogenous c-Src. Recruitment of Fyn requires the palmitoylation site near the N-terminus and addition of that site to c-Src enables it to support a rigidity response. In all cases, the rigidity response correlates with the recruitment of the Src family kinase to early adhesions. The stretch-activated substrate of Fyn and c-Src, p130Cas, is also required for a rigidity response and it is phosphorylated at the leading edge in a Fyn-dependent process. A possible mechanism for the fibronectin rigidity response involves force-dependent Fyn phosphorylation of p130Cas with rigidity-dependent displacement. With the greater displacement of Fyn from p130Cas on softer surfaces, there will be less phosphorylation. These studies emphasize the importance of force and nanometer-level movements in cell growth and function.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Division / physiology
  • Cells, Cultured
  • Crk-Associated Substrate Protein / metabolism*
  • Fibroblasts / cytology
  • Fibroblasts / physiology
  • Fibronectins / physiology*
  • Genes, Reporter
  • Humans
  • Palmitic Acid / metabolism
  • Protein Tyrosine Phosphatases / deficiency
  • Protein Tyrosine Phosphatases / genetics
  • Protein Tyrosine Phosphatases / metabolism*
  • Proto-Oncogene Proteins c-fyn / metabolism*
  • RNA, Small Interfering / metabolism
  • Receptor-Like Protein Tyrosine Phosphatases, Class 4
  • Receptors, Cell Surface / deficiency
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*

Substances

  • Crk-Associated Substrate Protein
  • Fibronectins
  • RNA, Small Interfering
  • Receptors, Cell Surface
  • Palmitic Acid
  • FYN protein, human
  • Proto-Oncogene Proteins c-fyn
  • PTPRA protein, human
  • Protein Tyrosine Phosphatases
  • Receptor-Like Protein Tyrosine Phosphatases, Class 4