| First Author | Ren Q | Year | 2007 |
| Journal | Mol Biol Cell | Volume | 18 |
| Issue | 1 | Pages | 24-33 |
| PubMed ID | 17065550 | Mgi Jnum | J:121010 |
| Mgi Id | MGI:3709109 | Doi | 10.1091/mbc.E06-09-0785 |
| Citation | Ren Q, et al. (2007) Endobrevin/VAMP-8 is the primary v-SNARE for the platelet release reaction. Mol Biol Cell 18(1):24-33 |
| abstractText | 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. |
