Abstract
Exocytosis from the three granules of platelets (dense-core, alpha, and lysosome) is a key event in normal hemostasis. Defects in these processes lead to bleeding-time disorders, such as Hermansky-Pudlak and gray platelet syndromes (1–4). Conversely, hyperactive secretion causes inappropriate clot formation, leading to the occurrence of stroke or heart attack (5,6). These two examples of hypo- and hyperactive platelets underline the need to understand the molecular mechanisms that are required for the platelet-release reaction. Recent advances by several groups have elucidated at least some of the proteins required for platelet exocytosis. Soluble NSF attachment protein receptor (SNARE) proteins mediate platelet granule-plasma membrane fusion (reviewed in 7–9). These integral membrane proteins form heterotrimeric (or heterotetrameric) complexes that span the two bilayers of a membrane fusion junction (reviewed in 10,11). Proteins of the t-SNARE class (target membrane SNAREs), such as syntaxin 2 and SNAP-23, have been shown to be required for all three granule-release events (12–15). Syntaxin 4, however, participates only in alpha-granule and lysosome release (12–14). v-SNAREs (vesicle SNAREs), such as VAMP-3/hceb and VAMP-8/endobrevin, have been shown to be present in platelets (16,17) and have been implicated in alpha-granule and dense-core exocytosis (17,18). With the establishment of the SNAREs as the basic membrane fusion machinery for granule release, the focus now turns to SNARE regulatory molecules that control how the t- and v-SNAREs interact with each other. Molecules such as Munc18, DOC2, Munc13, Rab, and members of the synaptophysin/pantophysin families are present in platelets (T. W. Rutledge and S. W. Whiteheart, unpublished observations; T. D. Schraw and A. M. Bernstein, personal communications; 19–21) and may hold the key to the distinct regulation of each of the three platelet-secretion events.
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Rutledge, T.W., Whiteheart, S.W. (2004). Studies of Secretion Using Permeabilized Platelets. In: Gibbins, J.M., Mahaut-Smith, M.P. (eds) Platelets and Megakaryocytes. Methods In Molecular Biology™, vol 272. Humana Press. https://doi.org/10.1385/1-59259-782-3:109
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DOI: https://doi.org/10.1385/1-59259-782-3:109
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