Actin filaments and microtubule dual-granule transport in human adhered platelets: the role of α-dystrobrevins (original) (raw)

2010, British Journal of Haematology

The critical role of the platelet is to sense vascular damage and respond by secreting components that promote primary haemostasis and clot formation. Activated platelets initiate signalling cascades that lead to cytoskeletal reorganization , centralization of secretory granules, and exocytosis of small molecules and proteins from three classes of granules: dense core and a-granules and secretory lysosomes (Rendu & Brohard-Bohn, 2001). Platelet granules are the most prominent structural features, and upon activation, they coalesce in the centre of the platelet and fuse with the open canalicular system (OCS). The OCS represents a membrane reservoir that is evaginated onto the platelet surface during interaction with surfaces (Stenberg et al, 1984; Escolar et al, 1989), fusing with the plasma membrane (Ginsberg et al, 1980). The release of the granule contents into the OCS and their diffusion into the extracellular environment exert a paracrine role to activate other platelets in the immediate area that are critical to the formation of the haemostatic thrombus (Escolar & White, 1991; White & Escolar, 1991). Dense core granules mainly contain small molecules, such as adenosine diphosphate (ADP), serotonin and calcium, which are critical for further platelet activation and vasoconstriction. a-Granules represent the storage sites for a diverse set of proteins, such as platelet factor 4, von Willebrand factor, platelet-derived growth factor and P-selectin, which play roles in clot formation and initiating wound healing. Platelets also release lysosomal enzymes, such as cathepsins and hexosaminidase, which may play a role in clot remodelling or in further platelet activation (Anitua et al, 2004). To date, more than 300 proteins and small molecules have been