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PMID:18278053
Citation |
Moser, M, Nieswandt, B, Ussar, S, Pozgajova, M and Fässler, R (2008) Kindlin-3 is essential for integrin activation and platelet aggregation. Nat. Med. 14:325-30 |
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Abstract |
Integrin-mediated platelet adhesion and aggregation are essential for sealing injured blood vessels and preventing blood loss, and excessive platelet aggregation can initiate arterial thrombosis, causing heart attacks and stroke. To ensure that platelets aggregate only at injury sites, integrins on circulating platelets exist in a low-affinity state and shift to a high-affinity state (in a process known as integrin activation or priming) after contacting a wounded vessel. The shift is mediated through binding of the cytoskeletal protein Talin to the beta subunit cytoplasmic tail. Here we show that platelets lacking the adhesion plaque protein Kindlin-3 cannot activate integrins despite normal Talin expression. As a direct consequence, Kindlin-3 deficiency results in severe bleeding and resistance to arterial thrombosis. Mechanistically, Kindlin-3 can directly bind to regions of beta-integrin tails distinct from those of Talin and trigger integrin activation. We have therefore identified Kindlin-3 as a novel and essential element for platelet integrin activation in hemostasis and thrombosis. |
Links |
PubMed Online version:10.1038/nm1722 |
Keywords |
Animals; Chimera; Cytoskeletal Proteins/genetics; Cytoskeletal Proteins/metabolism; Gene Deletion; Hepatocytes/metabolism; Integrins/metabolism; Mice; Osteoporosis; Platelet Aggregation/physiology |
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Significance
Annotations
Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
---|---|---|---|---|---|---|---|---|
MOUSE:ITB3 |
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:Q8K1B8 |
F |
Seeded From UniProt |
complete | |
MOUSE:ITB1 |
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:Q8K1B8 |
F |
Seeded From UniProt |
complete | |
MOUSE:URP2 |
enables |
GO:0005178: integrin binding |
ECO:0000314: direct assay evidence used in manual assertion |
F |
Seeded From UniProt |
complete | ||
MOUSE:URP2 |
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:P09055 |
F |
Seeded From UniProt |
complete | |
MOUSE:URP2 |
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:O54890 |
F |
Seeded From UniProt |
complete | |
MOUSE:URP2 |
involved_in |
GO:0033622: integrin activation |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
MOUSE:URP2 |
involved_in |
GO:0070527: platelet aggregation |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
See also
References
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