Ca2+-regulated secretory granule exocytosis in pancreatic and parotid acinar cells

Abstract

Protein secretion from acinar cells of the pancreas and parotid glands is controlled by G-protein coupled receptor activation and generation of the cellular messengers Ca2+, diacylglycerol and cAMP. Secretory granule (SG) exocytosis shares some common characteristics with nerve, neuroendocrine and endocrine cells which are regulated mainly by elevated cell Ca2+. However, in addition to diverse signaling pathways, acinar cells have large ˜1 ! m diameter SGs (˜30 fold larger diameter than synaptic vesicles), respond to stimulation at slower rates (seconds versus milliseconds), demonstrate significant constitutive secretion, and in isolated acini, undergo sequential compound SG-SG exocytosis at the apical membrane. Exocytosis proceeds as an initial rapid phase that peaks and declines over 3 min followed by a prolonged phase that decays to near basal levels over 20-30 min. Studies indicates the early phase is triggered by Ca2+ and involves the SG proteins VAMP2 (vesicle associated membrane protein2), Ca2+-sensing protein synatotagmin 1 (syt1) and the accessory protein complexin 2. The molecular details for regulation of VAMP8-mediated SG exocytosis and the prolonged phase of secretion are still emerging. Here we review the known regulatory molecules that impact the sequential exocytic process of SG tethering, docking, priming and fusion in acinar cells.

Vesicle Associated Membrane Protein 8 (VAMP8)-mediated Zymogen Granule Exocytosis Is Dependent on Endosomal Trafficking via the Constitutive-Like Secretory Pathway

“…Digestive enzymes or zymogens are condensed in the trans-Golgi and emerge in the cytoplasm as large immature secretory granules that then undergo a poorly defined maturation process resulting in the formation of large (ϳ1-m diameter) zymogen secretory granules (ZGs). 3 The ZGs accumulate as a storage pool that undergoes exocytosis over the next 2-24 h in response to hormone/ neurotransmitter stimulation of G-protein-coupled receptors. As is well accepted in all cells, exocytosis is mediated by SNARE complex assembly composed of vesicle-associated membrane protein (VAMP) or vSNAREs on ZGs that interact with plasma membrane (PM) target or tSNAREs of the syntaxin and SNAP25 families (2).…”

Chorein Sensitive Dopamine Release from Pheochromocytoma (PC12) Cells

“…In pancreatic acinar cell granule membranes, VAMP8 interacts with syntaxins 2 and 3 as well as SNAP-23 [23]. VAMP8 participates in the formation and is required for fusion of pancreatic acinar cell granules [23,28], which are significantly smaller in VAMP8 knockout mice than in wild type mice [23]. …”

Skeletal muscle as an endocrine organ: Role of [Na+]i/[K+]i-mediated excitation-transcription coupling

“…Exocytosis consists of multiple kinetically defined stages such as recruitment, targeting, tethering and docking of secretory vesicles with the sarcolemma, priming the fusion machinery and finally membrane fusion. The final stage is triggered by Ca 2+ and involves several secretory vesicle proteins including Ca 2+ -sensing protein synaptotagmin 1 (SYT1) 94 . These data suggest that elevation of [Ca 2+ ] i in contracting muscle may affect myokine secretion independently on regulation of their transcription and translation (Fig.…”