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: 4.47). 04/2007; 18(3):1056-63. DOI: 10.1091/mbc.E06-10-0974
Source: PubMed


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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    • "Vesicle-associated membrane protein 8 (VAMP8) was immnostained to evaluate the occupied pattern of secretory vesicles (SVs) in the acinar cells of specimens. VAMP8 was previously shown to be enriched on the membranes of zymogen granules [26]. The primary antibody used for immunostaining was a rabbit monoclonal antibody against VAMP8 (Abcam, UK). "
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    ABSTRACT: Tears are secreted from the lacrimal gland (LG), a dysfunction in which induces dry eye, resulting in ocular discomfort and visual impairment. Honey bee products are used as a nutritional source in daily life and medicine; however, little is known about their effects on dry eye. The aim of the present study was to investigate the effects of honey bee products on tear secretion capacity in dry eye. We selected raw honey, propolis, royal jelly (RJ), pollen, or larva from commercially available honey bee products. Tear secretion capacity was evaluated following the oral administration of each honey bee product in a rat blink-suppressed dry eye model. Changes in tear secretion, LG ATP content, and LG mitochondrial levels were measured. RJ restored the tear secretion capacity and decrease in LG ATP content and mitochondrial levels to the largest extent. Royal jelly can be used as a preventative intervention for dry eye by managing tear secretion capacity in the LG.
    PLoS ONE 09/2014; 9(9):e106338. DOI:10.1371/journal.pone.0106338 · 3.23 Impact Factor
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    • "1A, C and 3C), as well as in a previous one [16]. Although gene knockout studies clearly demonstrated that VAMP8 plays an important role in exocrine secretion [12] [13], the ISO and/or CyD treatment did not significantly increase the level of SNAP23-VAMP8 complex (Figs. 1C and 3C), suggesting the following two possibilities; (1) a large stable pool of SNAP23–VAMP8 complex exists on the intracellular membranes of rat parotid glands and thus a small transient increase in the SNARE complex on the plasma membrane would be masked; and (2) the interaction between SNAP23 and VAMP8 is not critical for ISO-stimulated exocytosis from the parotid gland. "
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    ABSTRACT: The exocytosis of salivary proteins is mainly regulated by cAMP, although soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs), which mediate cAMP-dependent exocytic membrane fusion, have remained unidentified. Here we examined the effect of isoproterenol (ISO) and cytochalasin D (CyD) on the level of SNARE complexes in rat parotid glands. When SNARE complexes were immunoprecipitated by anti-SNAP23, the coprecipitation of VAMP2 was significantly increased in response to ISO and/or CyD, although the coprecipitation of VAMP8 or syntaxin 4 was scarcely augmented. These results suggest that the SNAP23-VAMP2 interaction plays a key role in cAMP-mediated exocytosis from parotid glands. STRUCTURED SUMMARY OF PROTEIN INTERACTIONS: Snap23physically interactswithVamp8,Vamp3andSyn-4byanti bait coimmunoprecipitation(View Interaction:1,2,3)Vamp2physically interactswithSyn-4,Syn-3andSnap23byanti bait coimmunoprecipitation(View interaction)Syn-3physically interactswithSnap23byanti bait coimmunoprecipitation(View interaction)Vamp2physically interactswithSnap23andSyn-4byanti bait coimmunoprecipitation(View interaction)Snap23physically interactswithVamp8,Syn-4andVamp2byanti bait coimmunoprecipitation(View Interaction:1,2).
    FEBS letters 02/2013; 587(6). DOI:10.1016/j.febslet.2013.01.039 · 3.17 Impact Factor
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    • "In previous reports, VAMP8 and Rab3D immunostaining was detected in the vicinity of the apical membrane and cytoplasm of normal lacrimal gland epithelia. Wang et al. detected VAMP8 immunostaining near the apical membrane in normal mouse lacrimal glands [25]. Evans et al. detected Rab3D immunostaining at the subapical region in normal rabbit lacrimal glands [30]. "
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    ABSTRACT: Previous observations in a rat model of a non-Sjögren's syndrome (non-SS) type of dry eye seen in users of visual display terminals (VDT) indicated that secretory vesicle (SV) accumulation in the lacrimal gland epithelia contributes to the condition. Here, to examine this possibility in humans, we compared the lacrimal gland histology and percent SV area in the cytoplasm of acinar epithelial cells using light microscopy and transmission electron microscopy, in patients with VDT work-related non-SS dry-eye (VDT group), SS-induced dry-eye, and autopsied normal controls. In addition, the VAMP8 (vesicle-associated membrane protein 8, an exocrine-pathway molecule) and Rab3D (mature vesicle marker) were histochemically examined in lacrimal gland tissue sections. The lacrimal gland acini were larger in the VDT group than in the SS group, and the percent SV area was significantly higher in the VDT group than in the normal controls (P = 0.021) or SS group (P = 0.004). Immunostaining revealed abnormal distributions of VAMP8 in the VDT and SS groups. Rab3D was more strongly expressed in the cytoplasm of acinar epithelial cells in the VDT group than in that of normal controls. The duration of VDT use was significantly longer in the VDT group than in the other groups. These findings suggest that excessive SV accumulation in the acinar epithelia may contribute to the reduced tear secretion in VDT users.
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