Secretory granule neuroendocrine protein

The SNAREs involved in the fusion of synaptic vesicles and of secretory granules in neuroendocrine cells, referred to as neuronal SNAREs, have been intensely studied and serve as a paradigm for all SNAREs. They include syntaxin 1A and SNAP-25 at the presynaptic membrane and synaptobrevin 2 (also referred to as VAMP 2) at the vesicle membrane. Their importance for synaptic neurotransmission is documented by the fact that the block in neurotransmitter release caused by botulinum and tetanus neurotoxins is due to proteolysis of the neuronal SNAREs (Schiavo et al. 2000). Genetic deletion of these SNAREs confirmed their essential role in the last steps of neurotransmitter release. Intriguingly, analysis of chromaffin cells from KO mice lacking synaptobrevin or SNAP-25 showed that these proteins can be at least partially substituted by SNAP-23 and cellubrevin, respectively (Sorensen et al. 2003 Borisovska et al. 2005), i.e., the corresponding SNAREs involved in constitutive exocytosis. 

Chromogranins are a family of proteins that are major components of the secretory granules of most neuroendocrine cells. 

Figure 5 Proteomics reveals functional secretory vesicle protein systems for neuropeptide biosynthesis, storage, and secretion. Chromaffin secretory vesicles (also known as chromaffin granules) were isolated and subjected to proteomic analyses of proteins in the soluble and membrane components of the vesicles. Protein systems in secretory vesicle function consisted of those for 1) production of hormones, neurotransmitters, and neuromodulatory factors, 2) generating selected internal vesicular conditions for reducing condition, acidic pH conditions maintained by ATPases, and chaperones for protein folding, and 3) vesicular trafficking mechanisms to allow the mobilization of secretory vesicles for exocytosis, which uses proteins for nucleotide-binding, calcium regulation, and vesicle exocytosis. These protein systems are coordinated to allow the secretory vesicle to synthesize and release neuropeptides for cell-cell communication in the control of neuroendocrine functions.

Monoamines share the acid environment of the storage granule matrix with ATP, peptides, and proteins, the most well known of which are the chromogranins. The chro-mogranins are ubiquitous components of secretory vesicles and their widespread presence among endocrine tissue has led to their measurement in plasma as useful albeit relatively nonspecific markers of neuroendocrine tumors, including pheochromocytomas and carcinoid tumors. 

Chromogranin A belongs to a family of acidic secretory proteins associated with dense core granules in a variety of endocrine and neuroendocrine cells (41). A lymphocyte surface marker, Leu7/NHK, cross-reacts with related epitope on the plasma membrane of PNEC and NEB (42). The other NEB cell surface markers include neural adhesion molecule (NCAM) and related epitope MOC-1, originally identified in the small cell lung carcinoma cell line (43,44). 

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