Kindlin-2 controls bidirectional signaling of integrins.
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.
Montanez
Eloi
E
Department of Molecular Medicine, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
Ussar
Siegfried
S
Schifferer
Martina
M
Bösl
Michael
M
Zent
Roy
R
Moser
Markus
M
Fässler
Reinhard
R
D000199:Actins / Q000378:metabolism; D000818:Animals; D001755:Blastocyst; D016466:CHO Cells; D002448:Cell Adhesion / Q000235:genetics; D006224:Cricetinae; D003412:Cricetulus; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020964:Embryo Loss / Q000235:genetics; D004622:Embryo, Mammalian; D004707:Endoderm / Q000502:physiology; D016023:Integrins / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011108:Polymers / Q000378:metabolism; D011485:Protein Binding; D015398:Signal Transduction / Q000235:genetics; D016608:Talin / Q000502:physiology
D000199:Actins; D003598:Cytoskeletal Proteins; D016023:Integrins; D009124:Muscle Proteins; D011108:Polymers; D016608:Talin; C527802:kindlin-2 protein, mouse