Background: Members of the regulator of G-protein signaling (RGS) family inhibit G-protein coupled receptor signaling by modulating G-protein activity. In platelets, there are 3 different RGS isoforms that are expressed at the protein level, including RGS16. Recently, we have shown that CXCL12 regulates platelet function via RGS16. However, the role of RGS16 in platelet function and thrombus formation is poorly defined. Methods and Results: We used a genetic knockout mouse model approach to examine the role(s) of RGS16 in platelet activation by using a host of in vitro and in vivo assays. We observed that agonist-induced platelet aggregation, secretion, and integrin activation were much more pronounced in platelets from the RGS16 knockout (Rgs16−/−) mice relative to their wild type (Rgs16+/+) littermates. Furthermore, the Rgs16−/− mice had a markedly shortened bleeding time and were more susceptible to vascular injury–associated thrombus formation than the controls. Conclusions: These findings support a critical role for RGS16 in regulating hemostatic and thrombotic functions of platelets in mice. Hence, RGS16 represents a potential therapeutic target for modulating platelet function.
- regulator of G-protein signaling
- signal transduction
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine