VAMP8/endobrevin as a general vesicular SNARE for regulated exocytosis of the exocrine system

VAMP8/endobrevin as a general vesicular SNARE for regulated exocytosis of the exocrine system
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DOI:
10.1091/mbc.e06-10-0974
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发表时间:
2007-03-01
影响因子:
3.3
通讯作者:
Hong, Wanjin
Hong, Wanjin
中科院分区:
生物学3区
文献类型:
--
作者:
Wang, Cheng-Chun;Shi, Hong;Hong, Wanjin

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尽管最近已证明VAMP 8/endobrevin是胰腺外分泌腺泡细胞酶原颗粒的主要囊泡陷阱(v-SNARE),但大多数外分泌组织调节分泌的分子机制仍然难以捉摸。在这篇文章中,我们已经描述了VAMP 8在整个外分泌系统中的作用。免疫组织化学研究表明,VAMP 8在所有检查的外分泌组织中表达,如唾液腺、泪腺、汗腺、皮脂腺、乳腺和前列腺。在VAMP 8缺失小鼠的唾液腺和泪腺中观察到严重异常。突变唾液腺积累淀粉酶和碳酸酐酶VI。电子显微镜检查发现,在突变腮腺和泪腺的腺泡细胞分泌颗粒的积累。在VAMPS的情况下,毛果芸香碱刺激的唾液蛋白分泌受到损害。在突变泪腺中观察到蛋白质聚集体。VAMP 8可以与syntaxin 4和SNAP-23相互作用。这些结果表明,VAMP 8可能作为一个v-SNARE调节整个外分泌系统的分泌。
The molecular mechanism governing the regulated secretion of most exocrine tissues remains elusive, although VAMP8/endobrevin has recently been shown to be the major vesicular SNARE (v-SNARE) of zymogen granules of pancreatic exocrine acinar cells. In this article, we have characterized the role of VAMP8 in the entire exocrine system. Immunohistochemical studies showed that VAMP8 is expressed in all examined exocrine tissues such as salivary glands, lacrimal (tear) glands, sweat glands, sebaceous glands, mammary glands, and the prostate. Severe anomalies were observed in the salivary and lacrimal glands of VAMP8-null mice. Mutant salivary glands accumulated amylase and carbonic anhydrase VI. Electron microscopy revealed an accumulation of secretory granules in the acinar cells of mutant parotid and lacrimal glands. Pilocarpine-stimulated secretion of saliva proteins was compromised in the absence of VAMPS. Protein aggregates were observed in mutant lacrimal glands. VAMP8 may interact with syntaxin 4 and SNAP-23. These results suggest that VAMP8 may act as a v-SNARE for regulated secretion of the entire exocrine system.