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

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 FA‐PtdIns(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 .