Molecular dissection of alpha- and dense-core granule secretion of platelets.

Upon activation, platelets release many active substances stored in alpha- and dense-core granules. However, the molecular mechanisms governing the regulated exocytosis are not yet fully understood. We have established an assay system using streptolysin-O-permeabilized platelets to analyze the Ca2+-induced secretions of von Willebrand factor stored in alpha-granules and [3 H]5-hydroxytryptamine (5-HT) in dense-core granules. Using the assay, we found that small GTPase Rab4 regulates alpha-, but not dense-core, granule secretion in platelets. Furthermore, we purified a cytosolic essential protein and currently are analyzing its function.