Recombinant scinderin, an F-actin severing protein, increases calcium-induced release of serotonin from permeabilized platelets, an effect blocked by two scinderin-derived actin-binding peptides and phosphatidylinositol 4,5-bisphosphate.

In response to vessel injury or exposure to different substances, platelets undergo activation which consists of shape changes, formation of cellular pseudopodia, aggregation, and secretion. These dramatic changes are accompanied by cycles of actin depolymerization and polymerization. Previous work has shown the presence in platelets of gelsolin and scinderin, two Ca(2+)-dependent F-actin severing proteins. Recent published evidence suggests that scinderin is a component of the exocytotic machinery in chromaffin cells. The present work describes the preparation of recombinant scinderin and peptides Sc-ABP1 and Sc-ABP2 with sequences corresponding to two actin-binding sites of scinderin. Recombinant scinderin and peptides Sc-ABP1 and Sc-ABP2 were tested for their effects on Ca(2+)-induced serotonin release from digitonin permeabilized platelets. The results indicated that recombinant scinderin potentiates Ca(2+)-evoked serotonin release, an effect blocked in the presence of Sc-ABP1, Sc-ABP2, exogenous gamma-actin, or the addition of phosphatidylinositol 4,5-bisphosphate (PIP2). In the presence of a mismatched peptide (MMP) the potentiating effect of recombinant scinderin was not affected. Moreover, Sc-ABP1, Sc-ABP2, and gamma-actin inhibited Ca(2+)-induced release of serotonin in the absence of recombinant scinderin, suggesting an inhibition of platelet endogenous scinderin. MMP was ineffective under these conditions. The results suggest that F-actin disassembly, perhaps at a specific site, is required for platelet secretion and that scinderin might be an important component of the exocytotic machinery in platelets.