VAMP8/Endobrevin as a General Vesicular SNARE for Regulated Exocytosis of the Exocrine System

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.

Vesicle-associated Membrane Protein 8 (VAMP8) Is a SNARE (Soluble N-Ethylmaleimide-sensitive Factor Attachment Protein Receptor) Selectively Required for Sequential Granule-to-granule Fusion

“…There is also a consensus that the R-SNAREs VAMP2 (26,32,33) and VAMP8 are both present (8,26,30,32) with a recent paper indicating these SNAREs might be separately located on different populations of granules (26). Finally, studies show that SNAP23 is present (23), although it has variously been localized to the cell membrane (30) or on the granule membrane (26).…”

Sdmg1 is a component of secretory granules in mouse secretory exocrine tissues

“…Sdmg1 in each of these secretory exocrine cells bears some resemblance to the subcellular localization of Vamp8, a SNARE associated with secretory granules in these cell types (Wang et al, 2004(Wang et al, , 2007.…”

“…During secretory granule exocytosis, there appears to be little diffusion from the secretory granule membrane into the plasma membrane and, once the secretory granule cargo is expelled, the membrane of the secretory granule remains distinct from the plasma membrane and is eventually endocytosed and recycled (Thorn et al, 2004). Around 80 -90% of all protein secretion in the secretory exocrine cells of the pancreas and parotid salivary gland occurs through secretory granule exocytosis (Van Nest et al, 1980;von Zastrow and Castle, 1987); therefore, proteins involved in the regulated secretory pathway are expressed at high levels in these secretory exocrine cells (Wang et al, 2004(Wang et al, , 2007.…”

Cell surface dynamics – how Rho GTPases orchestrate the interplay between the plasma membrane and the cortical cytoskeleton

“…The most common SNARE complex, which comprises the vesicleassociated membrane protein 2 (VAMP2) and the two tSNAREs syntaxin1 and SNAP25 in the plasma membrane, operates in the release of transmitters from neurons and neurosecretory cells (Jahn and Scheller, 2006;Malsam et al, 2008). In the acinar cells of salivary and other glands the vSNARE is VAMP8 (Wang et al, 2007). Tetanus-toxininsensitive VAMP (Ti-VAMP, also known as VAMP7), which is involved in the exocytosis of secretory lysosomes, also participates in neurite outgrowth and in various forms of endocytosis (Martinez-Arca et al, 2001;Danglot et al, 2010).…”