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β1 integrin-mediated signals are required for platelet granule secretion and hemostasis in mouse.
- Source :
-
Blood [Blood] 2013 Oct 10; Vol. 122 (15), pp. 2723-31. Date of Electronic Publication: 2013 Sep 04. - Publication Year :
- 2013
-
Abstract
- Integrins are critical for platelet adhesion and aggregation during arterial thrombosis and hemostasis. Although the platelet-specific αIIbβ3 integrin is known to be crucial for these processes, the in vivo role of β1 integrins is a matter of debate. Here we demonstrate that mice expressing reduced levels of β1 integrins or an activation-deficient β1 integrin show strongly reduced platelet adhesion to collagen in vitro and in a carotis ligation model in vivo. Interestingly, hypomorphic mice expressing only 3% of β1 integrins on platelets show normal bleeding times despite reduced platelet adhesion. The residual 3% of β1 integrins are able to trigger intracellular signals driving Rac-1-dependent granule release required for platelet aggregation and hemostasis. Our findings support a model, in which platelet β1 integrins serve as an important signaling receptor rather than an adhesion receptor in vivo and therefore promote β1 integrins as a promising and so far clinically unemployed antithrombotic target.
- Subjects :
- Actins metabolism
Animals
Cytoskeletal Proteins genetics
Cytoskeletal Proteins metabolism
Integrin beta1 genetics
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neuropeptides metabolism
Platelet Adhesiveness physiology
Protein Binding physiology
Thrombosis metabolism
rac1 GTP-Binding Protein metabolism
Blood Platelets metabolism
Hemostasis physiology
Integrin beta1 metabolism
Secretory Vesicles metabolism
Signal Transduction physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 122
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 24004668
- Full Text :
- https://doi.org/10.1182/blood-2013-06-508721