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PMID: 17065550 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Molecular biology of the cell ·Vol. 18 ·No. 1 ·2007-01-00 ·Pages 24-33

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

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.

MeSH Terms
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
Chemicals
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
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Ren Qiansheng
Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, KY 40536, USA.
Barber Holly Kalani
Crawford Garland L
Karim Zubair A
Zhao Chunxia
Choi Wangsun
Wang Cheng-Chun
Hong Wanjin
Whiteheart Sidney W
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.e06-09-0785
Published
2007-01-00
Epub
2006-00-25
Pages
24-33
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC1751319
Subset
IM
Grants
NHLBI NIH HHS · R01 HL056652 · United States
NHLBI NIH HHS · R01 HL091893 · United States
External Links
PubMed source DOI: 10.1091/mbc.e06-09-0785 PMC Full Text View journal details
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