期刊
MOLECULAR BIOLOGY OF THE CELL
卷 18, 期 1, 页码 24-33出版社
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E06-09-0785
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- NHLBI NIH HHS [R01 HL056652, R01 HL091893] Funding Source: Medline
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL091893] Funding Source: NIH RePORTER
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.
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