Endobrevin/ VAMP-8 Is the Primary v-SNARE for the Platelet Release Reaction.
Platelet secretion is critical to hemostasis. Release of granular cargo is mediated by soluble NSF attachment protein receptors (SNAREs), but despite consensus on t-SNAREs usage, it is unclear which Vesicle Associated Membrane Protein (VAMPs: synaptobrevin/VAMP-2, cellubrevin/ VAMP-3, TI-VAMP/VAMP-7, and endobrevin/ VAMP-8) is required. We demonstrate that VAMP-8 is required for release from dense core granules, alpha granules, and lysosomes. Platelets from VAMP-8(-/-) mice have a significant defect in agonist-induced secretion, though signaling, morphology, and cargo levels appear normal. In contrast, VAMP-2(+/-), VAMP-3(-/-), and VAMP-2(+/-)/VAMP-3(-/-) platelets showed no defect. Consistently, tetanus toxin had no effect on secretion from permeabilized mouse VAMP-3(-/-) platelets or human platelets, despite cleavage of VAMP-2 and/or -3. Tetanus toxin does block the residual release from permeabilized VAMP-8(-/-) platelets, suggesting a secondary role for VAMP-2 and/or -3. These data imply a ranked redundancy of v-SNARE usage in platelets and suggest that VAMP-8(-/-) mice will be a useful in vivo model to study platelet exocytosis in hemostasis and vascular inflammation.[1]References
- Endobrevin/VAMP-8 Is the Primary v-SNARE for the Platelet Release Reaction. Ren, Q., Barber, H.K., Crawford, G.L., Karim, Z.A., Zhao, C., Choi, W., Wang, C.C., Hong, W., Whiteheart, S.W. Mol. Biol. Cell (2007) [Pubmed]
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