Abstract
Rho GTPases are critical for platelet function. Although the roles of RhoA, Rac and Cdc42 are characterized, platelets express other Rho GTPases, whose activities are less well understood. This review summarizes our understanding of the roles of platelet Rho GTPases and focuses particularly on the functions of Rif and RhoG. In human platelets, Rif interacts with cytoskeleton regulators including formins mDia1 and mDia3, whereas RhoG binds SNARE-complex proteins and cytoskeletal regulators ELMO and DOCK1. Knockout mouse studies suggest that Rif plays no critical functions in platelets, likely due to functional overlap with other Rho GTPases. In contrast, RhoG is essential for normal granule secretion downstream of the collagen receptor GPVI. The central defect in RhoG−/− platelets is reduced dense granule secretion, which impedes integrin activation and aggregation and limits platelet recruitment to growing thrombi under shear, translating into reduced thrombus formation in vivo. Potential avenues for future work on Rho GTPases in platelets are also highlighted, including identification of the key regulator for platelet filopodia formation and investigation of the role of the many Rho GTPase regulators in platelet function in both health and disease.
Highlights
The activities of Rho Ras homology family GTPase (GTPase) proteins are central to many of the processes that underpin the physiological and pathological roles of platelets [1]
The interaction of Rho in filopodia (Rif) with the formins has been documented in other cell types, our work suggests Rif is able to interact with mDia1 and mDia3 in platelets, which hints at its function
Both studies demonstrated that integrin activation, aggregation, α and dense granule secretion in response to GPVI agonists are significantly decreased in RhoG−/− platelets, whereas responses to agonists of the protease activated receptor (PAR) are normal
Summary
Rho GTPases are critical for platelet function. The roles of RhoA, Rac and Cdc are characterized, platelets express other Rho GTPases, whose activities are less well understood. This review summarizes our understanding of the roles of platelet Rho GTPases and focuses on the functions of Rif and RhoG. Rif interacts with cytoskeleton regulators including formins mDia and mDia, whereas RhoG binds SNARE-complex proteins and cytoskeletal regulators ELMO and DOCK1. Knockout mouse studies suggest that Rif plays no critical functions in platelets, likely due to functional overlap with other Rho GTPases. Potential avenues for future work on Rho GTPases in platelets are highlighted, including identification of the key regulator for platelet filopodia formation and investigation of the role of the many Rho GTPase regulators in platelet function in both health and disease.
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