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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Available from: Cheng-Chun Wang, Jul 07, 2015
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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. "
    Crosstalk and Integration of Membrane Trafficking Pathways, 04/2012; , ISBN: 978-953-51-0515-2
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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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    ABSTRACT: Mucin secretion is an innate defence mechanism, which is noxiously upregulated in obstructive lung diseases (e.g. chronic obstructive pulmonary disease (COPD), cystic fibrosis and asthma). Mucin granule exocytosis is regulated by specific protein complexes, but the SNARE exocytotic core has not been defined in airway goblet cells. In this study, we identify VAMP8 as one of the SNAREs regulating mucin granule exocytosis. VAMP8 mRNA was present in human airway and lung epithelial cells, and deep-sequencing and expression analyses of airway epithelial cells revealed that VAMP8 transcripts were expressed at 10 times higher levels than other VAMP mRNAs. In human airway epithelial cell cultures and freshly excised tissues, VAMP8 immunolocalised mainly to goblet cell mucin granules. The function of VAMP8 in airway mucin secretion was tested by RNA interference techniques. Both VAMP8 short interfering RNAs (siRNAs) and short hairpin RNAs (shRNAs) reduced mucin secretion induced by PAR agonists, neutrophil elastase and ATP in two airway epithelial cell culture models. Notably, basal (non-agonist elicited) mucin secretion was also reduced in these experiments. VAMP8 knockdown was also effective in decreasing mucin secretion in airway epithelial cell cultures with induced mucous metaplasia/mucin hypersecretion. Unlike VAMP8 silencing, knockdown of VAMP2 or VAMP3 did not affect mucin secretion. Importantly, in VAMP8 knock-out (KO) mice with IL-13-induced mucous metaplasia, mucin content in the bronchoalveolar lavage (BAL) and ATP-stimulated mucin secretion in the trachea were reduced compared to WT-matched littermates. Our data indicate that VAMP8 is an essential SNARE in airway mucin granule exocytosis. Reduction of VAMP8 activity/expression may provide a novel therapeutic target to ameliorate airway mucus obstruction in lung diseases.
    The Journal of Physiology 12/2011; 590(Pt 3):545-62. DOI:10.1113/jphysiol.2011.222091 · 4.54 Impact Factor
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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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    ABSTRACT: Casein micelles and fat globules are essential components of milk and are both secreted at the apical side of mammary epithelial cells during lactation. Milk fat globules are excreted by budding, being enwrapped by the apical plasma membrane, while caseins contained in transport vesicles are released by exocytosis. Nevertheless, the molecular mechanisms governing casein exocytosis are, to date, not fully deciphered. SNARE proteins are known to take part in cellular membrane trafficking and in exocytosis events in many cell types and we therefore attempted to identify those relevant to casein secretion. With this aim, we performed a detailed analysis of their expression by RT-PCR in both whole mouse mammary gland and in purified mammary acini at various physiological stages, as well as in the HC11 cell line. The expression of some regulatory proteins involved in SNARE complex formation such as Munc-13, Munc-18 and complexins was also explored. The amount of certain SNAREs appeared to be regulated depending on the physiological stage of the mammary gland. Co-immunoprecipitation experiments indicated that SNAP-23 interacted with syntaxin-6, -7 and -12, as well as with VAMP-3, -4 and -8 in mammary epithelial cells during lactation. Finally, the subcellular localisation of candidate SNAREs in these cells was determined both by indirect immunofluorescence and immunogold labelling. The present work provides important new data concerning SNARE proteins in mammary epithelial cells and points to SNAP-23 as a potential central player for the coupling of casein and milk fat globule secretion during lactation.
    European journal of cell biology 02/2011; 90(5):401-13. DOI:10.1016/j.ejcb.2011.01.002 · 3.70 Impact Factor

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