Disease relevance of SNAP23

• Within the syntaxin family, syntaxin 4 interacted with SNAP23 and all vesicle-associated membrane proteins (VAMPs) examined, except tetanus neurotoxin insensitive VAMP (TI-VAMP) [1].
• Here we report the generation of isoform-specific antibodies to SNAP-23 cloned from human melanoma cells, and their use in detecting the expression and localization of the endogenous SNAP-23 protein in several tissues and cell lines [2].
• Potential involvement of galectin-3 and SNAP23 in Aeromonas hydrophila cytotoxic enterotoxin-induced host cell apoptosis [3].

High impact information on SNAP23

• After relocation, SNAP-23 is required for exocytosis, implying a crucial role in promoting membrane fusion [4].
• Relocation of the t-SNARE SNAP-23 from lamellipodia-like cell surface projections regulates compound exocytosis in mast cells [4].
• In contrast, addition of PIP2 to Stx4/SNAP23 vesicles inhibited the fusion reaction, and its addition to VAMP2 vesicles was stimulatory [5].
• Addition of PA to Stx4/SNAP23 vesicles markedly enhanced the fusion rate, whereas its addition to VAMP2 vesicles was inhibitory [5].
• CFTR chloride channels are regulated by a SNAP-23/syntaxin 1A complex [6].

Biological context of SNAP23

• Exocytosis was rescued by expressing toxin-resistant SNAP25 or wild-type SNAP23, which is naturally toxin-resistant [7].
• Synaptosome-associated protein of 23 kDa (SNAP23) is a target SNARE previously identified at the plasma membrane, where it is involved in exocytotic membrane fusion [8].
• In support of separate binding sites on heavy chain for light chain and SNAPs, a complex of heavy and light chains was observed to interact with SNAP25 and SNAP23 [9].
• The SNAP23 gene has eight exons, with the initiation codon located in exon 2, and maps to the human chromosome 15q21-22 region [10].
• RESULTS: Nucleotide sequences obtained from PCR products exhibited nearly identical (>95%) homology with reported sequences for human SNAP-23 and syntaxin-4 [11].

Anatomical context of SNAP23

• We suggest that syntaxin 4, SNAP23, and VAMP8 may be involved in regulation of mast cell exocytosis [1].
• Vimentin filaments in fibroblasts are a reservoir for SNAP23, a component of the membrane fusion machinery [8].
• Here we show that SNAP23 associates with vimentin filaments in a Triton X-100 insoluble fraction in fibroblasts in primary culture and HeLa cells [8].
• In this study, we show that combinatorial soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes with vesicle-associated membrane proteins (VAMPs), 23-kDa synaptosome-associated protein (SNAP-23), and syntaxin 4 underlie the differential mobilization of granules in human neutrophils [12].
• Using the yeast two-hybrid system, we have identified a 23-kDa protein from human B lymphocytes (termed SNAP-23) that binds tightly to multiple syntaxins and synaptobrevins/VAMPs in vitro [13].

Associations of SNAP23 with chemical compounds

• Here, we have employed cysteine mutants of SNAP25/SNAP23, which have modified affinities for raft domains, to examine whether raft association of these proteins is important for the regulation of exocytosis [7].
• A dominant-negative variant of SNAP-23 decreases the cell surface expression of the neuronal glutamate transporter EAAC1 by slowing constitutive delivery [14].
• CFTR-mediated chloride currents are inhibited by introducing excess SNAP-23 into HT29-Cl.19A epithelial cells [6].
• Antibodies against SNAP-23 inhibited Ca(++) and GTP-gamma-S-induced exocytosis of CD67-enriched specific granules, but they hardly affected exocytosis of the CD63-enriched azurophilic granules, when introduced into electropermeabilized neutrophils [15].
• SNAP-23 cleavage is inhibited by calpeptin, calpastatin, calpain inhibitor IV, and E-64d, but not by caspase 3 inhibitor III or cathepsin inhibitor I. When tested for their effect on secretion, none of the calpain-specific inhibitors significantly affected release of soluble components from any of the three platelet granule storage pools [16].

Physical interactions of SNAP23

• Expression of a dominant-negative variant of SNAP-23 that lacks a domain required for SNARE complex assembly decreased the fraction of EAAC1 found on the cell surface and decreased total EAAC1 expression, while two control constructs had no effect [14].
• Conversely, CFTR activity is stimulated by a SNAP-23 antibody that blocks the binding of this t-SNARE to the CFTR amino-terminal tail [6].
• In vitro binding studies established that SNAP-23 binds to syntaxin 6 [15].
• Despite this, essentially all syntaxin 4 and most of VAMP-2 in these rafts were present in SNARE complexes containing SNAP-23, while essentially none of these complexes were present in nonraft membranes [17].

Regulatory relationships of SNAP23

• SNAP-23 is the ubiquitously expressed homologue of the neuronal SNAP-25, which functions in synaptic vesicle fusion [18].
• SNAP-23 mutants that mimic phosphorylation at Ser23/Thr24 inhibited syntaxin 4 interactions, whereas a phosphorylation mutant of Ser161 had only minor effects [19].
• These data suggest that SNAP-23 preferentially regulates plasma membrane-vesicle fusion events while SNAP-29 plays a role in the maintenance of various intracellular protein trafficking pathways [20].

Other interactions of SNAP23

• We studied the N-terminal coiled-coil domain of SNAP-23 (SNAP-23N), a non-neuronal homologue of SNAP-25, and its interaction with other coiled-coil domains [21].
• Third, E. chaffeensis also inhibited the gene transcription of RAB5A, SNAP23, and STX16, which are involved in membrane trafficking [22].
• The dominant-negative variant of SNAP-23 also slowed the rate of EAAC1 delivery to the plasma membrane [14].
• SNAP-23 physically associates with CFTR by binding to its amino-terminal tail, a region that modulates channel gating [6].
• SNAP-23 was translocated to the cell surface, colocalizing with syntaxin 6, on neutrophil activation [15].

Analytical, diagnostic and therapeutic context of SNAP23

• METHODS: Human peripheral blood eosinophils (>97%) from atopic subjects were subjected to RT-PCR and sequence analysis by using specific primers for SNAP-23 and syntaxin-4 [11].
• We now report the molecular cloning and characterization of rat SNAP-23, a ubiquitously expressed homologue of the essential neuronal SNARE protein SNAP-25 (synaptosomal-associated protein of 25 kDa) [23].
• Immunoblot and immunofluorescence analyses revealed that SNAP-23 is located predominantly in the plasma membrane of 3T3-L1 adipocytes incubated in the absence or presence of insulin [24].
• We investigated intracellular localisation of syntaxins 2, 3 and 4 and SNAP-23, which are thought to be target membrane (t)-SNAREs, in rat parotid gland by Western blotting and immunocytochemistry [25].
• Immunocytochemistry revealed SNAP-23 labeling at both the apex and the cytoplasm of collecting duct principal cells [26].

References