Endobrevin/VAMP-8 is the primary v-SNARE for the platelet release reaction
Endobrevin/VAMP-8 is the primary v-SNARE for the platelet release reaction
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DOI：
10.1091/mbc.e06-09-0785
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发表时间：
2007-01-01
影响因子：
3.3
通讯作者：
Whiteheart, Sidney W.
中科院分区：
文献类型：
--
作者：
Ren, Qiansheng;Barber, Holly Kalani;Whiteheart, Sidney W.
血小板的分泌是止血的关键。颗粒货物的释放是由可溶性NSF附着蛋白受体(SNARs)介导的，但尽管对t-SNARs的使用达成了共识，但尚不清楚需要哪种囊泡相关膜蛋白(VAMPS：synaptobrevin/VAMP-2、cell ubrevin/VAMP-3、TI-VAMP/VAMP-7和endobrevin/VAMP-8)。我们证明VAMP-8是从致密的核心颗粒、α颗粒和溶酶体中释放所必需的。来自VAMP-8(-/-)小鼠的血小板在激动剂诱导的分泌方面存在显著缺陷，尽管信号、形态和货物水平看起来正常。相反，VAMP-2(+/-)、VAMP-3(-/-)和VAMP-2(+/-/)VAMP-3(-/-)血小板无缺陷。破伤风毒素对通透性小鼠VAMP-3(-/-)血小板或人血小板的分泌无影响，尽管VAMP-2和/或-3被裂解。破伤风毒素可阻断VAMP-8(-/-)通透性血小板的残余释放，提示VAMP-2和/或-3可能起次要作用。这些数据表明，VAMP-8(-/-)小鼠在血小板中使用v-SNARE是一种有序的冗余，并将成为研究血小板在止血和血管炎症中的排泄作用的有用的体内模型。
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.