Kindlin-2 controls bidirectional signaling of integrins (original) (raw)

  1. Eloi Montanez1,3,
  2. Siegfried Ussar1,3,
  3. Martina Schifferer1,
  4. Michael Bösl1,
  5. Roy Zent2,
  6. Markus Moser1, and
  7. Reinhard Fässler1,4
  8. 1 Department of Molecular Medicine, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany;
  9. 2 Division of Nephrology, Department of Medicine, Vanderbilt Medical Center and Veterans Affairs Hospital, Nashville, Tennessee 37232, USA
  10. ↵3 These authors contributed equally to this work.

Abstract

Control of integrin activation is required for cell adhesion and ligand-induced signaling. Here we report that loss of the focal adhesion protein Kindlin-2 in mice results in peri-implantation lethality caused by severe detachment of the endoderm and epiblast from the basement membrane. We found that Kindlin-2-deficient cells were unable to activate their integrins and that Kindlin-2 is required for talin-induced integrin activation. Furthermore, we demonstrate that Kindlin-2 is required for integrin outside-in signaling to enable firm adhesion and spreading. Our findings provide evidence that Kindlin-2 is a novel and essential element of bidirectional integrin signaling.

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