Distinct focal adhesion protein modules control different aspects of mechanotransduction

J Cell Sci. 2017 May 1;130(9):1612-1624. doi: 10.1242/jcs.195362. Epub 2017 Mar 16.


Focal adhesions (FAs) are macromolecular complexes that regulate cell adhesion and mechanotransduction. By performing fluorescence recovery after photobleaching (FRAP) and fluorescence loss after photoactivation (FLAP) experiments, we found that the mobility of core FA proteins correlates with their function. Structural proteins such as tensin, talin and vinculin are significantly less mobile in FAs than signaling proteins such as FAK (also known as PTK2) and paxillin. The mobilities of the structural proteins are directly influenced by substrate stiffness, suggesting that they are involved in sensing the rigidity of the extracellular environment. The turnover rates of FAK and paxillin, as well as kindlin2 (also known as FERMT2), are not influenced by substrate stiffness. By using specific Src and FAK inhibitors, we reveal that force-sensing by vinculin occurs independently of FAK and paxillin phosphorylation. However, their phosphorylation is required for downstream Rac1-driven cellular processes, such as protrusion and cell migration. Overall, we show that the FA is composed of different functional modules that separately control mechanosensing and the cellular mechano-response.

Keywords: FAK; Focal adhesion; Mechanotransduction; Paxillin; Talin; Vinculin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement
  • Extracellular Matrix / metabolism
  • Fluorescence Recovery After Photobleaching
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism
  • Focal Adhesions / metabolism*
  • Mechanotransduction, Cellular*
  • Mice
  • Models, Biological
  • NIH 3T3 Cells
  • Paxillin / metabolism
  • Phosphorylation
  • Phosphotyrosine / metabolism
  • Protein Transport
  • Pseudopodia / metabolism
  • Signal Transduction
  • Vinculin / metabolism
  • src-Family Kinases / metabolism


  • Paxillin
  • Vinculin
  • Phosphotyrosine
  • Focal Adhesion Protein-Tyrosine Kinases
  • src-Family Kinases