| 1581071 | A second SNARE role for exocytic SNAP25 in endosome fusion. | Aikawa Y, etal., Mol Biol Cell. 2006 May;17(5):2113-24. Epub 2006 Feb 15. | Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins play key roles in membrane fusion, but their sorting to specific membranes is poorly understood. Moreover, individual SNARE proteins can function in multiple membrane fusion events dependent upon their trafficking itinerary. Synaptosome-associated protein of 25 kDa (SNAP25) is a plasma membrane Q (containing glutamate)-SNARE essential for Ca2+-dependent secretory vesicle-plasma membrane fusion in neuroendocrine cells. However, a substantial intracellular pool of SNAP25 is maintained by endocytosis. To assess the role of endosomal SNAP25, we expressed botulinum neurotoxin E (BoNT E) light chain in PC12 cells, which specifically cleaves SNAP25. BoNT E expression altered the intracellular distribution of SNAP25, shifting it from a perinuclear recycling endosome to sorting endosomes, which indicates that SNAP25 is required for its own endocytic trafficking. The trafficking of syntaxin 13 and endocytosed cargo was similarly disrupted by BoNT E expression as was an endosomal SNARE complex comprised of SNAP25/syntaxin 13/vesicle-associated membrane protein 2. The small-interfering RNA-mediated down-regulation of SNAP25 exerted effects similar to those of BoNT E expression. Our results indicate that SNAP25 has a second function as an endosomal Q-SNARE in trafficking from the sorting endosome to the recycling endosome and that BoNT E has effects linked to disruption of the endosome recycling pathway. | 16481393 | 2006-09-01 |
| 633971 | Identification of a novel SNAP25 interacting protein (SIP30). | Lee HK, etal., J Neurochem 2002 Jun;81(6):1338-47. | Soluble N -ethylmaleimide-sensitive factor attachment protein receptors (SNAREs), including synaptosome-associated proteins of 25 kDa (SNAP25), syntaxins, and vesicle-associated membrane proteins (VAMP), are essential for regulated exocytosis of synaptic vesicle s in neurotransmission. We identified a cDNA coding for a novel protein of 266 amino acids that we have named SIP30 (S NAP25 interacting protein of 30 kDa). SIP30 is expressed abundantly in brain and slightly in testis and kidney. In brain, SIP30 is highly expressed in the inferior and superior colliculi, which contain important relay nuclei of the auditory and visual systems. GST-pull-down and immunoprecipitation assays showed direct binding of SIP30 to SNAP25. Although SIP30 does not directly interact with syntaxin based on pull-down assays, syntaxin does co-immunoprecipitate with SIP30 suggesting that syntaxin is indirectly associated with SIP30, perhaps through SNAP25. | 12068081 | 2002-08-01 |
| 8553247 | Type VI adenylyl cyclase regulates neurite extension by binding to Snapin and Snap25. | Wu CS, etal., Mol Cell Biol. 2011 Dec;31(24):4874-86. doi: 10.1128/MCB.05593-11. Epub 2011 Oct 10. | 3'-5'-Cyclic AMP (cAMP) is an important second messenger which regulates neurite outgrowth. We demonstrate here that type VI adenylyl cyclase (AC6), an enzyme which catalyzes cAMP synthesis, regulates neurite outgrowth by direct interaction with a binding protein (Snapin) of Snap25 t:700;'>Snap25 at the N terminus of AC6 (AC6-N). We first showed that AC6 expression increased during postnatal brain development. In primary hippocampal neurons and Neuro2A cells, elevated AC6 expression suppressed neurite outgrowth, whereas the downregulation or genetic removal of AC6 promoted neurite extension. An AC6 variant (AC6-N5) that contains the N terminus of AC5 had no effect, indicating the importance of AC6-N. The downregulation of endogenous Snapin or the overexpression of a Snapin mutant (Snap(Delta33-51)) that does not bind to AC6, or another Snapin mutant (Snapin(S50A)) that does not interact with Snap25, reversed the inhibitory effect of AC6. Pulldown assays and immunoprecipitation-AC assays revealed that the complex formation of AC6, Snapin, and Snap25 is dependent on AC6-N and the phosphorylation of Snapin. The overexpression of Snap25 completely reversed the action of AC6. Collectively, in addition to cAMP production, AC6 plays a complex role in modulating neurite outgrowth by redistributing localization of the SNARE apparatus via its interaction with Snapin. | 21986494 | 2011-05-01 |
| 11530379 | Synaptosome-associated protein 25 (SNAP25) synthesis in terminal buttons of mouse motor neuron. | Islamov RR, etal., Dokl Biochem Biophys. 2015;464:272-4. doi: 10.1134/S1607672915050026. Epub 2015 Oct 31. | Previously, we formulated the hypothesis of compartmentalized protein synthesis in axons of motor neurons. In the axon hillock, along the entire length of the axon and in its ending, specific proteins are locally synthesized, which ensure the function of each compartment. In support of this hypothes is, in this work we studied the local protein synthesis in mouse motor nerve ending. | 26518545 | 1000-08-01 |
| 11057052 | Gbetagamma Binds to the Extreme C Terminus of SNAP25 to Mediate the Action of Gi/o-Coupled G Protein-Coupled Receptors. | Zurawski Z, etal., Mol Pharmacol. 2016 Jan;89(1):75-83. doi: 10.1124/mol.115.101600. Epub 2015 Oct 30. | Gi/o-coupled G protein-coupled receptors can exert an inhibitory effect on vesicle release through several G protein-driven mechanisms, more than one of which may be concurrently present in individual presynaptic terminals. The synaptosomal-associated protein of 25 kDa (SNAP25 '>SNAP25) is a key downstream effector of Gbetagamma subunits. It has previously been shown that proteolytic cleavage of SNAP25 by botulinum toxin A reduces the ability of Gbetagamma to compete with the calcium sensor synaptotagmin 1 (Syt1) for binding to SNAP25 in a calcium-dependent manner. These truncated SNAP25 proteins sustain a low level of exocytosis but are unable to support serotonin-mediated inhibition of exocytosis in lamprey spinal neurons. Here, we generate a SNAP25 extreme C-terminal mutant that is deficient in its ability to bind Gbetagamma while retaining normal calcium-dependent Syt1 binding to soluble N-ethylmaleimide attachment protein receptor (SNARE) and vesicle release. The SNAP25Delta3 mutant, in which residue G204 is replaced by a stop codon, features a partial reduction in Gbeta1gamma2 binding in vitro as well as a partial reduction in the ability of the lamprey 5-hydroxytryptamine1b-type serotonin receptor to reduce excitatory postsynaptic current amplitudes, an effect previously shown to be mediated through the interaction of Gbetagamma with SNAP25. Syt1 calcium-dependent binding to SNAP25Delta3 was reduced by a small extent compared with the wild type. We conclude that the extreme C terminus of SNAP25 is a critical region for the Gbetagamma-SNARE interaction. | 26519224 | 2016-04-01 |
| 11573812 | NOS1 and SNAP25 polymorphisms are associated with Attention-Deficit/Hyperactivity Disorder symptoms in adults but not in children. | Salatino-Oliveira A, etal., J Psychiatr Res. 2016 Apr;75:75-81. doi: 10.1016/j.jpsychires.2016.01.010. Epub 2016 Jan 18. | Several investigations documented that Attention-Deficit/Hyperactivity Disorder (ADHD) is better conceptualized as a dimensional disorder. At the same time, the disorder seems to have different neurobiological underpinnings and phenotypic presentation in children compared to adults. Neurodevelopment al genes could explain, at least partly these differences. The aim of the present study was to examine possible associations between polymorphisms in SNAP25, MAP1B and NOS1 genes and ADHD symptoms in Brazilian samples of children/adolescents and adults with ADHD. The youth sample consisted of 301 patients whereas the adult sample comprises 485 individuals with ADHD. Diagnoses of ADHD and comorbidities were based on the Diagnostic and Statistical Manual of Mental Disorders-4th edition criteria. The Swanson, Nolan and Pelham Scale-Version IV (SNAP-IV) was applied by psychiatrists blinded to genotype. The total SNAP-IV scores were compared between genotypes. Impulsivity SNAP-IV scores were also compared according to NOS1 genotypes. Adult patients homozygous for the C allele at SNAP25 rs8636 showed significantly higher total SNAP-IV scores (F = 11.215; adjusted P-value = 0.004). Impulsivity SNAP-IV scores were also significantly different according to NOS1 rs478597 polymorphisms in adults with ADHD (F = 6.282; adjusted P-value = 0.026). These associations were not observed in children and adolescents with ADHD. These results suggest that SNAP25 and NOS1 genotypes influence ADHD symptoms only in adults with ADHD. Our study corroborates previous evidences for differences in the genetic contribution to adult ADHD compared with childhood ADHD. | 26821215 | 2016-04-01 |
| 11556946 | Synaptosomal Protein of 25 kDa (Snap25) Polymorphisms Associated with Glycemic Parameters in Type 2 Diabetes Patients. | Al-Daghri NM, etal., J Diabetes Res. 2016;2016:8943092. doi: 10.1155/2016/8943092. Epub 2015 Dec 8. | A possible role of Snap25 polymorphisms in type 2 diabetes mellitus (T2DM) was evaluated by analyzing three SNPs within intron 1 in a region known to affect the gene expression in vitro. Genomic DNA from 1019 Saudi individuals (489 confirmed T2DM and 530 contro ls) was genotyped for SNPs rs363039, rs363043, and rs363050 in Snap25 using the TaqMan Genotyping Assay. Significantly higher levels of fasting glucose and HbA1c were detected in T2DM patients carrying the rs363050 (AG/GG) genotypes compared to the (AA) genotype (f = 4.41, df = 1, and p = 0.03 and f = 5.31, df = 1, and p = 0.03, resp.). In these same patients, insulin levels were significantly decreased compared to the (AA) individuals (f = 7.29, df = 1, and p = 0.009). Significant associations were detected between rs363050 (AG/GG) genotypes and increasing fasting glucose levels (p = 0.01 and OR: 1.05), HbA1c levels (OR: 5.06 and p = 0.02), and lower insulinemia (p = 0.03 and OR: 0.95) in T2DM patients. The minor Snap25 rs363050 (G) allele, which results in a reduced expression of Snap25, is associated with altered glycemic parameters in T2DM possibly because of reduced functionality in the exocytotic machinery leading to suboptimal release of insulin. | 26779543 | 1000-11-01 |
| 11532639 | Mutant SNAP25B causes myasthenia, cortical hyperexcitability, ataxia, and intellectual disability. | Shen XM, etal., Neurology. 2014 Dec 9;83(24):2247-55. doi: 10.1212/WNL.0000000000001079. Epub 2014 Nov 7. | OBJECTIVE: To identify and characterize the molecular basis of a syndrome associated with myasthenia, cortical hyperexcitability, cerebellar ataxia, and intellectual disability. METHODS: We performed in vitro microelectrode studies of neuromuscular transmission, performed exome and Sanger sequencing , and analyzed functional consequences of the identified mutation in expression studies. RESULTS: Neuromuscular transmission at patient endplates was compromised by reduced evoked quantal release. Exome sequencing identified a dominant de novo variant, p.Ile67Asn, in SNAP25B, a SNARE protein essential for exocytosis of synaptic vesicles from nerve terminals and of dense-core vesicles from endocrine cells. Ca(2+)-triggered exocytosis is initiated when synaptobrevin attached to synaptic vesicles (v-SNARE) assembles with SNAP25B and syntaxin anchored in the presynaptic membrane (t-SNAREs) into an alpha-helical coiled-coil held together by hydrophobic interactions. Pathogenicity of the Ile67Asn mutation was confirmed by 2 measures. First, the Ca(2+) triggered fusion of liposomes incorporating v-SNARE with liposomes containing t-SNAREs was hindered when t-SNAREs harbored the mutant SNAP25B moiety. Second, depolarization of bovine chromaffin cells transfected with mutant SNAP25B or with mutant plus wild-type SNAP25B markedly reduced depolarization-evoked exocytosis compared with wild-type transfected cells. CONCLUSION: Ile67Asn variant in SNAP25B is pathogenic because it inhibits synaptic vesicle exocytosis. We attribute the deleterious effects of the mutation to disruption of the hydrophobic alpha-helical coiled-coil structure of the SNARE complex by replacement of a highly hydrophobic isoleucine by a strongly hydrophilic asparagine. | 25381298 | 2014-09-01 |
