Platelet Rho GTPases-a focus on novel players, roles and relationships.
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.
*Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, U.S.A.
Robert
R
Goggs
†School of Physiology and Pharmacology, Faculty of Medical and Veterinary Sciences, University of Bristol, Bristol BS8 1TD, U.K.
Christopher M
CM
Williams
‡School of Biochemistry, Faculty of Medical and Veterinary Sciences, University of Bristol, Bristol BS8 1TD, U.K.
Harry
H
Mellor
†School of Physiology and Pharmacology, Faculty of Medical and Veterinary Sciences, University of Bristol, Bristol BS8 1TD, U.K.
Alastair W
AW
Poole
D000818:Animals; D001792:Blood Platelets / Q000201:enzymology* / Q000378:metabolism*; D006801:Humans; D015539:Platelet Activation / Q000502:physiology; D010974:Platelet Aggregation / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D020741:rho GTP-Binding Proteins / Q000502:physiology*
D020741:rho GTP-Binding Proteins