PKCδ Regulates Platelet Activity through the Inhibition of VASP-Mediated Filopodia Formation.

Filopodia are finger-like protrusions that play a crucial role in the guidance of cells through their extracellular and cellular environment. Blood platelets provide an essential early response system in haemostasis and arterial thrombosis and display a rapid and dramatic generation of filopodia upon activation, which play an essential role regulating their adhesive events leading to platelet aggregation. Here we report a novel and unexpected control mechanism for this explosive cellular rearrangement. Using pharmacological and genetic approaches we show that the novel isoform of protein kinase C, PKCδ, is a critical negative regulator of actin polymerization, filopodia formation and platelet aggregation. We show that PKCδ interacts with vasodilator-stimulated phosphoprotein (VASP), a major regulator of actin cytoskeleton dynamics, and regulates VASP phosphorylation. VASP is shown to be necessary for the PKCδ-dependent regulation of actin polymerization, filopodia formation and platelet aggregation. We therefore propose a causative link between the functional interaction of PKCδ with VASP and the role of the kinase as modulator of platelet activity.