Article

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

Institute of Molecular and Cell Biology, Singapore 138673, Singapore.
Molecular Biology of the Cell (Impact Factor: 4.55). 04/2007; 18(3):1056-63. DOI: 10.1091/mbc.E06-10-0974
Source: PubMed

ABSTRACT 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 VAMP8. 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.

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    • "Importantly, populations of vesicles are distinguished by the presence of specific combinations of coat proteins, such as clathrin, Adaptor Proteins (AP1-4), FAPP1/2, GGAs, ARF, v-snares, and synaptotagmin. In the parotid gland, VAMP2, VAMP8, syntaxin4/6, and synaptotagmin decorate the cytoplasmic side of secretory granules (Fujita-Yoshigaki et al. 2006; Wang et al. 2007). These different coat proteins on different vesicles direct the vesicles to the correct target membranes. "
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    • "Initially, VAMP8 was identified as an endosomal v-SNARE, but more recent data demonstrated that it might not be essential for endocytosis (Wang et al. 2004). Immunohistochemical studies show that VAMP8 is expressed in exocrine tissues such as pancreatic, salivary, lachrymal, sweat, sebaceous, mammary and prostate glands (Wang et al. 2007). A major physiological role of VAMP8 has been recently revealed by studies in the VAMP8 knockout (KO) mouse, which indicated that VAMP8 is a crucial vesicular SNARE in regulated exocytosis from exocrine cells (Wang et al. 2004). "
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    • "To date, only a few studies have directly addressed the functions of SNAREs in MECs. One of these suggests that VAMP-8 (Vesicle-Associated Membrane Protein-8) may be involved in casein secretion (Wang et al., 2007). Moreover, the expression of the small GTPase Rab3A, as well as some SNAREs and regulatory proteins, has been observed in the mammary-derived MCF-7 and HC11 cell lines (Vadlamudi et al., 2000). "
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