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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Actins / metabolism
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Animals
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Blastocyst
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CHO Cells
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Cell Adhesion / genetics
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Cricetinae
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Cricetulus
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Cytoskeletal Proteins / genetics
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Cytoskeletal Proteins / metabolism
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Cytoskeletal Proteins / physiology*
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Embryo Loss / genetics
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Embryo, Mammalian
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Endoderm / physiology
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Integrins / metabolism*
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Integrins / physiology
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Mice
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Mice, Knockout
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Muscle Proteins / genetics
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Muscle Proteins / metabolism
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Muscle Proteins / physiology*
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Polymers / metabolism
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Protein Binding
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Signal Transduction / genetics
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Talin / physiology
Substances
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Actins
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Cytoskeletal Proteins
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Integrins
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Muscle Proteins
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Polymers
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Talin
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kindlin-2 protein, mouse