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

Kyle R Legate, Seiichiro Takahashi, Navid Bonakdar, Ben Fabry, David Boettiger, Roy Zent, Reinhard Fässler

Author Affiliations

  1. Kyle R Legate1,
  2. Seiichiro Takahashi1,
  3. Navid Bonakdar2,
  4. Ben Fabry2,
  5. David Boettiger1,3,
  6. Roy Zent4 and
  7. Reinhard Fässler*,1
  1. 1 Department of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried, Germany
  2. 2 Center for Medical Physics and Technology, Department of Physics, University of Erlangen, Erlangen, Germany
  3. 3 Department of Microbiology, University of Pennsylvania, Philadelphia, PA, USA
  4. 4 Division of Nephrology, Department of Medicine, Vanderbilt Medical Center and Veterans Affairs Hospital, Nashville, TN, USA
  1. *Corresponding author. Department of Molecular Medicine, Max Planck Institute of Biochemistry, Am Klopferspitz 18, Martinsried 82152, Germany. Tel.: +49 898 578 2072; Fax: +49 898 578 2422; E‐mail: faessler{at}biochem.mpg.de
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Abstract

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)P2). Although PtdIns(4,5)P2 regulates the function of several FA‐associated molecules, the role of the FA‐specific pool of PtdIns(4,5)P2 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)P2 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)P2 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)P2 rather than bulk membrane PtdIns(4,5)P2.

  • Received February 26, 2011.
  • Accepted August 19, 2011.
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