Integrin adhesion and force coupling are independently regulated by localized PtdIns(4,5)2 synthesis

EMBO J. 2011 Nov 16;30(22):4539-53. doi: 10.1038/emboj.2011.332.


The 90-kDa isoform of the lipid kinase PIP kinase Type I γ (PIPKIγ) localizes to focal adhesions (FAs), where it provides a local source of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P(2)). Although PtdIns(4,5)P(2) regulates the function of several FA-associated molecules, the role of the FA-specific pool of PtdIns(4,5)P(2) is not known. We report that the genetic ablation of PIPKIγ specifically from FAs results in defective integrin-mediated adhesion and force coupling. Adhesion defects in cells deficient in FAPtdIns(4,5)P(2) synthesis are corrected within minutes while integrin-actin force coupling remains defective over a longer period. Talin and vinculin, but not kindlin, are less efficiently recruited to new adhesions in these cells. These data demonstrate that the specific depletion of PtdIns(4,5)P(2) from FAs temporally separates integrin-ligand binding from integrin-actin force coupling by regulating talin and vinculin recruitment. Furthermore, it suggests that force coupling relies heavily on locally generated PtdIns(4,5)P(2) rather than bulk membrane PtdIns(4,5)P(2).

Publication types

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

MeSH terms

  • Animals
  • Carrier Proteins / metabolism
  • Cell Adhesion / genetics
  • Cells, Cultured
  • Focal Adhesions / chemistry
  • Focal Adhesions / metabolism*
  • Integrins / metabolism*
  • Membrane Proteins / metabolism
  • Mice
  • Phosphatidylinositol 4,5-Diphosphate / biosynthesis*
  • Phosphatidylinositol 4,5-Diphosphate / metabolism
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Protein Binding
  • Talin / metabolism
  • Vinculin / metabolism


  • Carrier Proteins
  • Integrins
  • Membrane Proteins
  • Phosphatidylinositol 4,5-Diphosphate
  • Talin
  • kindlin-1 protein, mouse
  • Vinculin
  • Phosphotransferases (Alcohol Group Acceptor)
  • 1-phosphatidylinositol-4-phosphate 5-kinase