Neuroendocrine cell

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... 

Like all neuropeptides, NT is synthesized as part of a larger precursor that also contains neuromedin N (NN), a 6 amino acid neurotensin-like peptide (Table 1). Pro-NT/NN is processed in the regulated secretory pathway of neuroendocrine cells by prohormone convertases PCI, PC2 and PC5-A that belong to a larger family of proprotein convertases. Due to differential cleavage specificity and tissue distribution of the convertases, pro-NT/NN processing gives rise to approximately a 1 1 and a 5 1 ratio of NT over NN content in the brain and gut, respectively. The peptides are stored in secretory vesicles and released from neuroendocrine cells in a Ca2+-dependent manner. NT and NN actions are terminated by desensitization of the... 

Membrane-bound GTP rabs recruit effectors to the membrane. In neurons and neuroendocrine cells, the vesicle-associated Rab3 binds to rabphilin and to RIM. RIM is a component of the presynaptic cytomatrix and may thus serve as a docking receptor for synaptic vesicles at the active zone. 

Cl -channels are also present in neuroendocrine cells such as the AtT-20 pituitary cell line [30]. Ca -dependent and voltage-activated slow Cl -currents were found. These Cl -currents could subserve a role comparable to that of Cl -currents in renin-secreting cells or mast cells [13,14]. Along these lines, it has been speculated that the slow Cl inward currents may influence the firing rate of these neuroendocrine cells [30]. 

Cav1.3 t lD Cochlea, retina, neuroendocrine cells in the pancreas... 

Hearn, S.A. (1987) Electron microscopic localization of chromogranin A in osmium-fixed neuroendocrine cells with a protein A-gold technique./. Histochem. Cytochem. 35, 795-801. 

Other pinocytotic pathways also exist that do not depend on either caveolae or clathrin, although these are not as well defined [55]. Specific receptors continue to be internalized in the absence of clathrin or caveolin and these pathways can be monitored by following glycosyl phos-phatidylinositol (GPI (-anchored proteins. Nonclathrin, noncaveolin pathways may also be responsible for the reuptake of membrane in neuroendocrine cells after stimulated secretion. Some, but not all, of these pathways appear to require dynamin. 

However, an alternative pathway that bypasses clathrin-mediated endocytosis and EEs appears to be available as well. This model of endocytosis known as kiss and run or its variant kiss and stay have attracted increasing interest in recent years [74] (Fig. 9-9B). Kiss and run has been directly demonstrated with dense-core granules in neuroendocrine cells [84, 85], and this model would explain some observations that are not readily accommodated by the classical pathway. The kiss and run model proposes that neurotransmitters are released by a transient fusion pore, rather than by a complete fusion with integration of the synaptic vesicle components into the plasma membrane. Synaptic membrane proteins never lose their association and the vesicle reforms when the pore closes. As a result, the empty vesicle can be refilled and reused without going through clathrin-mediated endocytosis and sorting in the EEs. 

There are important differences between fast synaptic transmission at nerve terminals and the release of proteins and peptides from nerve terminals and neuroendocrine cells 177 Discrete steps in the regulated secretory pathway can be defined in neuroendocrine cells 177... 

Gastric neuroendocrine-cell neoplasia mainly in rats... 

C. Carcinoid tumors arise from neuroendocrine cells of the gut and secrete serotonin and gastrointestinal hormones, which activate the gastrointestinal tract and result in diarrhea. Most of these tumors have receptors for somatostatin, which inhibit secretion when activated, resulting in reduced activity of the gut. Octreotide is a stable analogue of... 

We have already discussed the co-occurrence of small amine and peptide neurotransmitters their release is normally Ca + dependent, and they operate through signal transmission. They are also capable of regulating each other s release and even the synthesis, clustering, and affinity of receptors. Neuroendocrine cells are capable of producing more than one peptide, and thus an amine-peptide as well as a peptide-peptide combination is possible. It is known, for instance, that the vagus nerve contains substance P, vasointestinal peptide, enkephalin, cholecystokinin, and somatostatin— peptides with a hybrid combination of neural and hormonal communication properties. 

Xue, Y., Lange, W., Smedts, F., Debruyne, F., de la Rosette, J., Schalken, J., and Verhofstad, A. 1998. A novel immunoenzymatic technique to demonstrate multiple antigens in cells based on selective destaining of substrate deposits and its application in characterizing the immunophenotype of neuroendocrine cells in the human prostate epithelium. Appl. Immunohistochem. 6 69-76. 

Stratified squamous to mucociliated epithelium with olfactory cells Mucociliated epithelium (ciliated, mucous cells, basal cells) smooth muscle cells fibroblasts neuroendocrine cells immune cells Mucociliated epithelium with Clara cells in distal bronchioles and alveolar ducts... 

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. 

Synaptobrevin 2 is a small protein composed of 118 amino acids. It contains a SNARE motif with a short N-terminal proline-rich extension but lacks an independently folded N-terminal domain. Like syntaxin 1, the protein possesses a C-terminal transmembrane domain that is connected to the SNARE motif by a short linker (Figure 1). Synaptobrevin is palmitoylated at cysteine residues close to its transmembrane domain. Synaptobrevin 2 is highly expressed in neurons and neuroendocrine cells, but unlike syntaxin 1 it is also present in many non-neuronal tissues albeit at low levels. 

Synaptotagmins comprise a small family of single-membrane spanning proteins that are expressed in neurons and neuroendocrine cells. So far 16 members have been identified in vertebrates (Craxton 2004). They contain an N-terminal transmembrane domain followed by a variable linker region and two C2 domains which are connected by a short linker (Stidhof 2002). Some synaptotagmins have additional short... 

Based on the results of a-LTX mutagenesis, strong correlation exists between pore formation and stimulation of Ca2+-dependent exocytosis from neuroendocrine cells. However, in some experiments with chromaffin cells, a-LTX action does not involve Ca2+ entry (Michelena et al. 1997). In addition, a-LTX sensitizes chromaffin cells to Ca2+ even when the cells are permeabilized and toxin pores should have no effect this involves protein kinase C (PKC) activation (Bittner and Holz 2000). Furthermore, the ability of a-LTXN4C to induce Ca2+-dependent exocytosis without forming pores implicates a stimulating mechanism other than pore formation. 

As a-LTXN4C (see Section 2.3) does not form pores, it probably stimulates exocy-tosis by receptor mediated signaling. Therefore, the activity of a-LTXN4C has been investigated in Ca2+-dependent and Ca2+-independent exocytosis from neurons and Ca2+-dependent exocytosis from neuroendocrine cells. 

Ahnert-Hilger G, Wiedenmann B (1994) Requirements for exocytosis in permeabilized neuroendocrine cells. Possible involvement of heterotrimeric G proteins associated with secretory vesicles. AnnNYAcad Sci 733 298-305... 

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