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Genes & Dev. 22 (10): 1325-1330

Copyright © 2008 by Cold Spring Harbor Laboratory Press.

RESEARCH COMMUNICATION

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

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.

Key Words: Integrin activation • Kindlin-2 • adhesion • mouse development • embryonic stem cells

Received for publication January 3, 2008. Accepted for publication March 10, 2008.

3 These authors contributed equally to this work.

4 Corresponding author.

E-MAIL faessler{at}biochem.mpg.de; FAX 49-89-8578-2422.

Supplemental material is available at http://www.genesdev.org.

Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.469408.

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