Neuroendocrine cells, secretory granule

While the basic features of SNARE assembly and disassembly provide a convenient framework for explaining how membrane fusion works, both the regulation of SNAREs and the molecular details of fusion are not well understood. Most is known about the neuronal SNAREs that mediate regulated membrane fusion of synaptic vesicles and of secretory granules in neuroendocrine cells. They include synaptobrevin2, localized to the synaptic vesicle, and SNAP25 ( SNAPs) and syntaxinlA, both of which are localized to the plasma... 

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. 

The capillary hemangioblastoma resembles an endocrine neoplasm (Fig. 20.56). It has close juxtaposition of capillary and stromal cells (see Table 20.7) and occasionally shows secretory granules or expresses erythropoietin. Its pink, vacuolated stromal cells often contain NSE, which is present in neuroendocrine cells. No gland of origin has been found. 

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). 

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.

---