Figure 1.

Platelet RhoGTPases regulate ROS formation. Platelet express the most well-known RhoGTPases family members Rac1, Cdc42 and RhoA that regulates actin reorganization within the platelet cytoskeleton. Rac1 and Cdc42 regulate lamellipodia and filopodia formation, while RhoA regulates stress fiber formation. In addition to these classical roles in platelet activity, RhoGTPases have been uncovered as regulators of reactive oxygen species (ROS) formation by modulating the NADPH oxidase complex. Rac1 regulates NADPH oxidase complex assembly by directly binding to p67^phox in response to thrombin, as well as GPVI and GPIb agonists. RhoA regulates thrombin-mediated ROS formation by inhibiting p47^phox phosphorylation, whereas a potential role for Cdc42 in directly regulating ROS formation remains to be identified. ROS generation triggers a positive feedback loop on platelet activation that promotes further ROS production and amplifies platelet recruitment, activation and aggregation, which ultimately leads to thrombus formation