Endobrevin/VAMP-8 is the primary v-SNARE for the platelet release reaction.

Abstract

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.

• Authors: Qiansheng Ren, Holly Kalani Barber, Garland L Crawford, Zubair A Karim, Chunxia Zhao, Wangsun Choi, Cheng-Chun Wang, Wanjin Hong, Sidney W Whiteheart
• Journal: Molecular biology of the cell (Mol Biol Cell) Vol. 18 Issue 1 Pg. 24-33 (Jan 2007) ISSN: 1059-1524 [Print] United States
• PMID: 17065550 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• R-SNARE Proteins
• SNARE Proteins
• Tetanus Toxin
• Vamp8 protein, mouse
• Vesicle-Associated Membrane Protein 2
• Vesicle-Associated Membrane Protein 3
• vesicle-associated membrane protein 2, mouse
• vesicle-associated membrane protein 3, mouse
• Adenosine Triphosphate
• Protein-Tyrosine Kinases
• Thrombin
• Metalloendopeptidases
• zinc-endopeptidase, tetanus neurotoxin
• Calcium

Topics

• Adenosine Triphosphate (metabolism)
• Animals
• Blood Platelets (drug effects, metabolism, ultrastructure)
• Calcium (metabolism)
• Exocytosis (drug effects)
• Humans
• Metalloendopeptidases (pharmacology)
• Mice
• Mice, Knockout
• Platelet Aggregation (drug effects)
• Protein-Tyrosine Kinases (metabolism)
• R-SNARE Proteins (deficiency, metabolism)
• SNARE Proteins (metabolism)
• Signal Transduction (drug effects)
• Tetanus Toxin (pharmacology)
• Thrombin (pharmacology)
• Vesicle-Associated Membrane Protein 2 (deficiency, metabolism)
• Vesicle-Associated Membrane Protein 3 (deficiency)