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Integrin adhesion and force coupling are independently regulated by localized PtdIns(4,5) 2 synthesis
Author(s) -
Legate Kyle R,
Takahashi Seiichiro,
Bonakdar Navid,
Fabry Ben,
Boettiger David,
Zent Roy,
Fässler Reinhard
Publication year - 2011
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2011.332
Subject(s) - vinculin , focal adhesion , integrin , microbiology and biotechnology , phosphatidylinositol , biology , actin , coupling (piping) , adhesion , actin cytoskeleton , kinase , cytoskeleton , signal transduction , biochemistry , chemistry , materials science , cell , organic chemistry , metallurgy
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 .