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.

journal_name

Mol Biol Cell

authors

Ren Q,Barber HK,Crawford GL,Karim ZA,Zhao C,Choi W,Wang CC,Hong W,Whiteheart SW

doi

10.1091/mbc.e06-09-0785

subject

Has Abstract

pub_date

2007-01-01 00:00:00

pages

24-33

issue

1

eissn

1059-1524

issn

1939-4586

pii

E06-09-0785

journal_volume

18

pub_type

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