1. β1 integrin-mediated signals are required for platelet granule secretion and hemostasis in mouse.
- Author
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Petzold T, Ruppert R, Pandey D, Barocke V, Meyer H, Lorenz M, Zhang L, Siess W, Massberg S, and Moser M
- 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
- 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.
- Published
- 2013
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