Disease relevance of Snap25

• Tetanus toxin (TeTx) and the various forms of botulinal neurotoxins (BoNT/A to BoNT/G) potently inhibit neurotransmission by means of their L chains which selectively proteolyze synaptic proteins such as synaptobrevin (TeTx, BoNT/B, BoNT/F), SNAP-25 (BoNT/A), and syntaxin (BoNT/C1) [1].
• Using patch clamp techniques, we have demonstrated that the activity of the K(DR) channel subtype, K(V)1.1, identified by its specific blocker dendrodotoxin-K, is inhibited by SNAP-25 in insulinoma HIT-T15 beta cells [2].
• In pheochromocytoma PC12 cells, SNAP-25 is phosphorylated at Ser(187), which lies in a region that is important for its function [3].
• METHODOLOGY AND RESULTS: High-efficiency infection of rat pancreatic acini in culture with these adenoviruses by subcellular fractionation showed that the overexpressed SNAP-23, SNAP-25, and their truncated mutant proteins were uniformly targeted to the zymogen granules and plasma membrane [4].
• We show here that BoNT/E, like BoNT/A, cleaves SNAP-25, as generated by in vitro translation or by expression in Escherichia coli [5].

Psychiatry related information on Snap25

• Neuronal Differentiation Is Accompanied by Increased Levels of SNAP-25 Protein in Fetal Rat Primary Cortical Neurons: Implications in Neuronal Plasticity and Alzheimer's Disease [6].
• The inhibition of SNAP-25 with intracerebroventricular antisense oligonucleotide caused a deficit in long- but not short-term memory for step-down inhibitory avoidance [7].
• The synaptic protein synaptosomal-associated protein-25 (SNAP25) is decreased whereas amphiphysin is phosphorylated after sleep deprivation [8].
• In a previous study, we showed that in the rat brain cortex a novel HCA extract (HCA-SX, Super CitriMax) increases the release/availability of radiolabeled 5-hydroxytryptamine or serotonin ([3H]-5-HT), a neurotransmitter implicated in the regulation of eating behavior and appetite control [9].

High impact information on Snap25

• Neurotransmitter exocytosis, a process mediated by a core complex of syntaxin, SNAP-25, and VAMP (SNAREs), is inhibited by SNARE-cleaving neurotoxins [10].
• Botulinum neurotoxin E inhibition of norepinephrine release in permeabilized PC12 cells can be rescued by adding a 65 aa C-terminal fragment of SNAP-25 (S25-C) [10].
• We report that SNAP-23, a t-SNARE related to SNAP-25, relocates in response to stimulation from plasma membrane lamellipodia-like projections to granule membranes in permeabilized mast cells [11].
• The binding of Hrs-2 to SNAP-25 is inhibited by calcium in the physiological concentration range that supports synaptic transmission [12].
• We report here that SNAP-25 is expressed in axonal growth cones during late stages of elongation and that selective inhibition of SNAP-25 expression prevents neurite elongation by rat cortical neurons and PC-12 cells in vitro and by amacrine cells of the developing chick retina in vivo [13].

Chemical compound and disease context of Snap25

• Cleavage of synaptobrevin and SNAP-25 by the neurotoxic clostridial proteases tetanus toxin and botulinum toxin A had no effect on assembly and disassembly of the 20S complex; however, the stability of its SDS-resistant SNARE core was compromised [14].
• These findings suggest that 1) SNC inhibits translocation of vesicles containing synaptophysin and SNAP-25, and 2) SNC reacts with cysteine residues in Gi/Go, causing inhibition of ADP-ribosylation by pertussis toxin [15].
• It is concluded that capsaicin induces release of substance P from dorsal root ganglion neurons via two mechanisms, one requiring extracellular Ca(2+) and the intact synaptosomal-associated protein 25 kDa (SNAP-25), and the other independent of extracellular Ca(2+) and not involving SNAP-25 [16].
• The effects of the increase of intracellular calcium, induced by membrane depolarization with 50 mM KCl, and arachidonic acid (AA) on the expression of 25-kD synaptosomal-associated protein (SNAP-25) were studied in cultured rat hippocampal and cerebellar explants, and PC12 rat pheochromocytoma cells, using immunoblot analysis [17].
• Both truncated SNAP-25 products inhibited depolarization-dependent glutamate release from hippocampal cultures and depressed synaptic transmission in Aplysia buccal ganglion cells [18].

Biological context of Snap25

• During neuronal exocytosis, the vesicle-bound soluble NSF attachment protein (SNAP) receptor (SNARE) synaptobrevin 2 forms complexes with the plasma membrane-bound SNAREs syntaxin 1A and SNAP25 to initiate the fusion reaction [19].
• Neuronal SNARE-proteins such as synaptobrevin, SNAP 25, and synaptotagmin are key players during neurosecretion [20].
• Synaptobrevin also interacts with the plasma membrane-associated proteins syntaxin and SNAP25, thereby forming the SNARE complex necessary for exocytotic membrane fusion [21].
• Since certain hormones under hypophyseal control play an essential role in determining chromaffin cell phenotype, the present study examined the effect of hypophysectomy on SNAP-25 expression [22].
• SNAP-25 C-terminal domains, SNAP-25(198-206) and SNAP-25(181-197), had no effect on Kv2.1 gating kinetics [23].

Anatomical context of Snap25

• SNAP-25 resides on the plasma membrane and interacts with syntaxin (a plasma membrane t-SNARE) and VAMP (a vesicle v-SNARE) to form a core protein complex thought to be an intermediate in a biochemical pathway that is essential for vesicular transport [12].
• As synaptobrevin and synaptophysin are localized mainly in transmitter-containing synaptic vesicles while SNAP-25 and syntaxin 1/HPC-1 are found in presynaptic plasma membranes, these results suggest differential involvement of synaptic components in AD [24].
• Estrogen down-regulates mRNA encoding the exocytotic protein SNAP-25 in the rat pituitary gland [25].
• SNAP-25 (25 kDa synaptosome-associated protein) is found in cells that release neurotransmitters and hormones, and plays a central role in the fusion of secretory vesicles with the plasma membrane [26].
• The synaptic membrane proteins syntaxin, 25K synaptosome-associated protein (SNAP25), and vesicle-associated membrane protein (VAMP)/synaptobrevin, are thought to form a synaptic core complex which mediates vesicle docking and membrane fusion [27].

Associations of Snap25 with chemical compounds

• Synaptic exocytosis requires the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins syntaxin 1, SNAP-25, and synaptobrevin (VAMP) [28].
• We now show that liposome fusion mediated by synaptic SNAREs is inhibited by botulinum neurotoxin E (BoNT/E) but can be rescued by supplementing the C-terminal portion of SNAP-25 [28].
• Previously, we reported that application of 4-aminopyridine to hippocampal slices resulted in a persistent potentiation of synaptic transmission and the induction of a short-lasting and specific 40-kDa complex composed of synaptosomal associated protein of 25 kDa (SNAP25) and caveolin1 [29].
• In contrast, subcutaneous injection of hypophysectomized rats with thyroid hormone decreased adrenal SNAP-25, demonstrating the potential importance of the pituitary-thyroid axis [22].
• Ca(2+) promotes the interaction of syt with anionic phospholipids and the target membrane SNAREs (t-SNAREs) SNAP-25 and syntaxin [30].

Physical interactions of Snap25

• In the neuron, the plasma membrane SNAREs syntaxin 1a and SNAP25 bind to VAMP2 found on neurotransmitter-containing vesicles [31].
• Thus, the synaptobrevin pool bound to synaptophysin is not available for binding to syntaxin I and SNAP-25, and vice versa [32].
• We now show that fragments containing the N- and C-terminal regions of the SNARE motif from syntaxin 1A bind SNAP-25 similarly [33].
• The tandem C2 domains of syt cooperate to mediate binding to syntaxin/SNAP-25; lengthening the linker that connects C2A and C2B selectively disrupts this interaction [34].
• Soluble N-ethylmaleimide-sensitive fusion protein (NSF) attachment protein receptor (SNARE) complexes composed of target (t-) SNAREs syntaxin and SNAP-25 and vesicle SNARE synaptobrevin play an essential role in neurosecretion [35].

Co-localisations of Snap25

• These data demonstrate the functional significance of SNAP-25 as a SNARE protein in the parietal cell and show the dynamic stimulation-associated redistribution of VAMP-2 from H,K-ATPase-rich tubulovesicles to co-localize with SNAP-25 on the apical plasma membrane [36].

Regulatory relationships of Snap25

• The granule maturation marker chromogranin A is expressed in chromaffin cells later than SNAP-25 [37].
• The data suggest that synaptobrevin, syntaxin, and SNAP-25 are subject to proteolytic modification by activated calpain in intact type II cells stimulated for secretion [38].

Other interactions of Snap25

• Antibodies against syntaxin 1, SNAP 25, and VAMP 2 (synaptobrevin) each immunoprecipitated a similar fraction (20-40%) of omega-conotoxin MVIIC receptors [39].
• So far palmitoylation of SNAP-25 and synaptotagmin 1 have been described in vivo [20].
• The results suggest that estrogen selectively regulates SNAP-25 transcription in the pituitary gland, but leaves VAMP-2, munc-18 and Hrs-2 mRNA levels unaffected [25].
• A recombinant, C-terminally His-tagged synaptobrevin fragment bound to nickel beads specifically bound synaptophysin, syntaxin and SNAP25 from vesicular detergent extracts [21].
• In defined reactions, the ubiquitous plasma membrane syntaxin isoforms, when in binary complexes with SNAP-25, readily bound vesicular synaptobrevin to form SDS-resistant SNARE (soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor) complexes implicated in membrane fusion [26].

Analytical, diagnostic and therapeutic context of Snap25

• Co-immunoprecipitation suggested that Csps occur in complexes containing synaptobrevin (VAMP), but not syntaxin 1, SNAP-25, nor P/Q-type calcium channels labeled with 125I-omega-conotoxin MVIIC [40].
• The proposed neuronal target (t)-membrane SNAREs, SNAP-25, and syntaxin isoforms 1-4 were also detected by Western blotting [41].
• In addition, SNAP-25 protein and mRNA levels were followed in adrenal gland extracts by immunoblotting and reverse transcription-polymerase chain reaction (RT-PCR) [37].
• In situ hybridization was used to examine whether SNAP-25 isoform mRNA expression may be altered by experimental manipulations [42].
• Adenohypophyses were studied by immunohistochemistry and immunoblot analysis using antibodies against SNAP-25, syntaxin-1 and TSH [43].

References