How platelet shape change initiated by a collagen-related peptide (CRP) specific for the GPVI/FcR gamma -chain complex (GPVI/FcR gamma -chain) is coupled to SLP-76, phosphoinositide (PI) 3-kinase, and gelsolin is reported. As shown by video microscopy, platelets rapidly round and grow dynamic filopodial projections that rotate around the periphery of the cell after they contact a CRP-coated surface. Lamellae subsequently spread between the projections. All the actin-driven shape changes require SLP-76 expression. SLP-76 is essential for the Ca++ mobilization induced by CRP, whereas PI 3-kinase only modulates it, The extension of lamellae requires net actin assembly and an exposure of actin filament barbed ends downstream of PI 3-kinase, Gelsolin expression is also required for the extension of lamellae, but not for the formation of filopodia, Altogether, the data describe the role of SLP-76 in the platelet activation initiated by GPVI/FcR gamma -chain and the roles of PI 3-kinase and gelsolin in lamellae spreading. (C) 2000 by The American Society of Hematology.