Disease relevance of Snap23

• In E. coli MPT83 was expressed as a 23kDa antigen whereas in the rapid growing mycobacterium Mycobacterium smegmatis the protein was expressed as a 25kDa protein indicating post-translational modification of the protein by M. smegmatis [1].

High impact information on Snap23

• To address this question, we examined neuroexocytosis from chromaffin cells of Snap25 null mice rescued by the two splice variants SNAP-25a and SNAP-25b and the ubiquitously expressed homolog SNAP-23 [2].
• Overexpression of SNAP-25a, SNAP-25b, and SNAP-23 resulted in three distinct phenotypes; SNAP-25b induced larger primed vesicle pools than SNAP-25a, whereas SNAP-23 did not support a standing pool of primed vesicles [2].
• Intriguingly, although the extra cysteine in SNAP-23 enhances its raft association, the phenylalanine at the same position in SNAP-25 acts to repress the raft association of this protein [3].
• SNAP-25 and its ubiquitously expressed homologue, SNAP-23, are SNARE proteins that are essential for regulated exocytosis in diverse cell types [3].
• Recent work has shown that SNAP-25 and SNAP-23 are partly localized in sphingolipid/cholesterol-rich lipid raft domains of the plasma membrane and that the integrity of these domains is important for exocytosis [3].

Biological context of Snap23

• Syndet is tightly bound to membranes, possibly by acylation within the cysteine-rich domain [4].
• Like many ubiquitously expressed housekeeping genes, the proximal promoter region for the mouse SNAP-23 gene lacks consensus TATA and CAAT boxes [5].
• The SNAP-23 gene spans 31kb of the mouse genome and consists of eight exons interrupted by seven introns [5].
• The SNAP-23 gene was localized to mouse chromosome 2 at band 2E5 using both fluorescence in-situ hybridization and radiation hybrid panel mapping studies [5].
• Analysis of syntaxin 4 and SNAP23, plasma membrane-localized target receptor proteins (t-SNAREs) for the GLUT4 vesicle, showed that they were not cell-surface targets of O-linked glycosylation [6].

Anatomical context of Snap23

• Immunofluorescence analysis revealed that SNAP-23 was clustered at the plasma membrane and almost completely segregated from the transferrin receptor [7].
• Here, we use combined membrane fractionation, detergent solubility, and sucrose gradient flotation to demonstrate that the large majority (>70%) of SNAP-23 and a significant proportion of syntaxin 4 ( approximately 35%) are associated with plasma membrane lipid rafts in 3T3-L1 adipocytes [7].
• We hypothesize that SNAP23 and its interaction with the cytoskeleton may be targets for regulation of GLUT-4 traffic [8].

Associations of Snap23 with chemical compounds

• Thus, the relative expression levels of SNAP-25 and SNAP-23 might control the mode (regulated vs. basal) of granule release by forming docking complexes at different Ca(2+) thresholds [9].
• Botulinum neurotoxin B inhibits insulin-stimulated glucose uptake into 3T3-L1 adipocytes and cleaves cellubrevin unlike type A toxin which failed to proteolyze the SNAP-23 present [10].
• A measurable fraction of SNAP23 was sedimented with cytoskeletal elements when extracted with Triton X-100, unlike VAMP-2 and syntaxin-4, which were exclusively soluble in detergent [8].
• A cytosolic 23kDa protein was initially purified from bovine brain and shown to bind phosphatidylethanolamine [11].
• Exocytosis of glutamate receptors to the dendritic surface occurs via a SNARE [soluble n-ethylmaleimide-sensitive factor attachment protein (SNAP) receptor]-dependent SNAP-23-mediated mechanism [12].

Physical interactions of Snap23

• This is the first localization of SNAP-23 within a polarized tissue and suggests that this t-SNAREs may interact with syntaxin-4 to mediate basolateral secretion [13].

Other interactions of Snap23

• Insulin stimulation had no effect on the plasma membrane raft association of SNAP-23 or syntaxin 4 but promoted VAMP2 insertion into plasma membrane rafts [7].
• Differential control of the releasable vesicle pools by SNAP-25 splice variants and SNAP-23 [2].
• The subcellular location of SNAP-23, SNAP-25, syntaxins 1 to 4, and vesicle-associated membrane protein (VAMP)-2 were explored using a laser scanning confocal imaging system [14].
• Mouse MTHFS has a molecular mass of 23kDa and is 84% identical in amino acid sequence to the human enzyme [15].

Analytical, diagnostic and therapeutic context of Snap23

• Microinjection of anti-Syndet antibodies into 3T3-L1 adipocytes, or incubation of permeabilized adipocytes with a synthetic peptide comprising the C-terminal 24 amino acids of Syndet, inhibited insulin-stimulated GLUT4 translocation to the cell surface by approximately 40% [16].

References