Abstract
Platelet activation at sites of vascular injury is essential for primary hemostasis, but also underlies arterial thrombosis leading to myocardial infarction or stroke1,2. Platelet activators such as adenosine diphosphate, thrombin or thromboxane A2 (TXA2) activate receptors that are coupled to heterotrimeric G proteins1,3. Activation of platelets through these receptors involves signaling through Gq, Gi and Gz (refs. 4–6). However, the role and relative importance of G12 and G13, which are activated by various platelet stimuli7,8,9, are unclear. Here we show that lack of Gα13, but not Gα12, severely reduced the potency of thrombin, TXA2 and collagen to induce platelet shape changes and aggregation in vitro. These defects were accompanied by reduced activation of RhoA and inability to form stable platelet thrombi under high shear stress ex vivo. Gα13 deficiency in platelets resulted in a severe defect in primary hemostasis and complete protection against arterial thrombosis in vivo. We conclude that G13-mediated signaling processes are required for normal hemostasis and thrombosis and may serve as a new target for antiplatelet drugs.
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Acknowledgements
We thank A. Rogatzki and A. Rippberger for expert technical help and B. Arnold for kind help with bone marrow transplantation experiments. This work was supported by the Deutsche Forschungsgemeinschaft and the Volkswagen Foundation.
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Moers, A., Nieswandt, B., Massberg, S. et al. G13 is an essential mediator of platelet activation in hemostasis and thrombosis. Nat Med 9, 1418–1422 (2003). https://doi.org/10.1038/nm943
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DOI: https://doi.org/10.1038/nm943
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