Kindlin-2 controls bidirectional signaling of integrins
- Eloi Montanez1,3,
- Siegfried Ussar1,3,
- Martina Schifferer1,
- Michael Bösl1,
- Roy Zent2,
- Markus Moser1, and
- Reinhard Fässler1,4
- 1 Department of Molecular Medicine, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany;
- 2 Division of Nephrology, Department of Medicine, Vanderbilt Medical Center and Veterans Affairs Hospital, Nashville, Tennessee 37232, USA
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↵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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Footnotes
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↵4 Corresponding author.
↵4 E-MAIL faessler{at}biochem.mpg.de; FAX 49-89-8578-2422.
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Supplemental material is available at http://www.genesdev.org.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.469408.
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- Received January 3, 2008.
- Accepted March 10, 2008.
- Copyright © 2008, Cold Spring Harbor Laboratory Press
