更新于：2024-11-01

SV2C

更新于：2024-11-01

基本信息

别名

KIAA1054、SV2C、synaptic vesicle glycoprotein 2C

简介

Plays a role in the control of regulated secretion in neural and endocrine cells, enhancing selectively low-frequency neurotransmission. Positively regulates vesicle fusion by maintaining the readily releasable pool of secretory vesicles. (Microbial infection) Possible receptor for C.botulinum neurotoxin type D (BoNT/D, botD); note that type D does not usually infect humans. (Microbial infection) Receptor for C.botulinum neurotoxin type A (BoNT/A, botA); the toxin probably binds via extracellular loop 4 (PubMed:27313224). Recognition by BoNT/A relies on both protein-protein and protein-N-glycosylation; glycosylation of Asn-559 increases its affinity for BoNT/A (PubMed:27313224). Also serves as a receptor for the closely related C.botulinum neurotoxin type A2; glycosylation is not essential but enhances the interaction (PubMed:29649119).

关联

100 项与 SV2C 相关的临床结果

登录后查看更多信息

100 项与 SV2C 相关的转化医学

登录后查看更多信息

0 项与 SV2C 相关的专利（医药）

登录后查看更多信息

项与 SV2C 相关的文献（医药）

2024-05-01·European Journal of Neuroscience

Synaptic vesicle glycoprotein 2C enhances vesicular storage of dopamine and counters dopaminergic toxicity

Article

作者: Johnson, Michelle A. ; Bradner, Joshua M. ; Egerton, Kristen Stout ; Dunn, Amy R. ; Miller, Gary W. ; Bucher, Meghan L. ; Burkett, James P.

AbstractDopaminergic neurons of the substantia nigra exist in a persistent state of vulnerability resulting from high baseline oxidative stress, high‐energy demand, and broad unmyelinated axonal arborisations. Impairments in the storage of dopamine compound this stress because of cytosolic reactions that transform the vital neurotransmitter into an endogenous neurotoxicant, and this toxicity is thought to contribute to the dopamine neuron degeneration that occurs Parkinson's disease. We have previously identified synaptic vesicle glycoprotein 2C (SV2C) as a modifier of vesicular dopamine function, demonstrating that genetic ablation of SV2C in mice results in decreased dopamine content and evoked dopamine release in the striatum. Here, we adapted a previously published in vitro assay utilising false fluorescent neurotransmitter 206 (FFN206) to visualise how SV2C regulates vesicular dopamine dynamics and determined that SV2C promotes the uptake and retention of FFN206 within vesicles. In addition, we present data indicating that SV2C enhances the retention of dopamine in the vesicular compartment with radiolabelled dopamine in vesicles isolated from immortalised cells and from mouse brain. Further, we demonstrate that SV2C enhances the ability of vesicles to store the neurotoxicant 1‐methyl‐4‐phenylpyridinium (MPP+) and that genetic ablation of SV2C results in enhanced 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced vulnerability in mice. Together, these findings suggest that SV2C functions to enhance vesicular storage of dopamine and neurotoxicants and helps maintain the integrity of dopaminergic neurons.

2024-04-01·Heliyon

Association analyses between the variants of SNAP25, SV2C and ST3GAL2 and the efficacy of botulinum toxin A in the treatment of the primary Meige syndrome

Article

作者: Chu, Lu-Lu ; Liu, Jing ; Xu, Ying-Ying ; Li, Kai ; Shen, Ting-Ting ; Luo, Wei-Feng ; Zhou, Xu-Ping ; Wu, Wen-Qi ; Li, Yang ; Liu, Chun-Feng ; Zhang, Qi-Lin

ObjectiveIndividual differences were observed in the clinical efficacy of Botulinum toxin A (BoNT-A) in the treatment of the primary Meige syndrome. Our study aimed to explore the potential associations between the clinical efficacy of BoNT-A in the treatment of the primary Meige syndrome and variants of SNAP25, SV2C and ST3GAL2, which are involving in the translocation of the BoNT-A in vivo.MethodsPatients with the primary Meige syndrome treated with BoNT-A were enrolled. Clinical efficacy was evaluated by the maximum improvement rate of motor symptoms and the duration of efficacy. Variants of SNAP25, SV2C and ST3GAL2 were obtained by Sanger sequencing. Another cohort diagnosed with primary cervical dystonia was also enrolled in the replication stage.ResultsAmong the 104 primary Meige syndrome patients, 80 patients (76.9%) had a good efficacy (the maximum improvement rate of motor symptoms ≥30%) and 24 (23. 1%) had a poor (the maximum improvement rate of motor symptoms <30%). As to the duration of efficacy, 52 patients (50.0%) had a long duration of efficacy (≥4 months), and 52 (50.0%) had a short (<4 months). In terms of primary Meige syndrome, SNAP25 rs6104571 was found associating with the maximum improvement rate of motor symptoms (Genotype: P = 0.02, OR = 0.26; Allele: P = 0.013, OR = 0.29), and SV2C rs31244 was found associating with the duration of efficacy (Genotype: P = 0.024, OR = 0.13; Allele: P = 0.012, OR = 0.13). Besides, we also conducted the association analyses between the variants and BoNT-A-related adverse reactions. Although, there was no statistical difference between the allele of SV2C rs31244 and BoNT-A-related adverse reactions, there was a trend (P = 0.077, OR = 2.56). In the replication stage, we included 39 patients with primary cervical dystonia to further expanding the samples' size. Among the 39 primary cervical dystonia patients, 25 patients (64.1%) had a good efficacy (the maximum improvement rate of motor symptoms ≥50%) and 14 (35.9%) had a poor (the maximum improvement rate of motor symptoms <50%). As to the duration of efficacy, 32 patients (82.1%) had a long duration of efficacy (≥6 months), and 7 (17.9%) had a short (<6 months). Integrating primary Meige syndrome and primary cervical dystonia, SV2C rs31244 was still found associating with the duration of efficacy (Genotype: P = 0.002, OR = 0. 23; Allele: P = 0.001, OR = 0. 25).ConclusionIn our study, SNAP25 rs6104571 was associated with the maximum improvement rate of motor symptoms in patients with primary Meige syndrome treated with BoNT-A, and patients carrying this variant had a lower improvement rate of motor symptoms. SV2C rs31244 was associated with duration of treatment in patients with primary Meige syndrome treated with BoNT-A and patients carrying this variant had a shorter duration of treatment. Patients with primary Meige syndrome carrying SV2C rs31244 G allele have an increase likelihood of BoNT-A-related adverse reactions. Involving 39 patients with primary cervical dystonia, the results further verify that SV2C rs31244 was associated with duration of treatment and patients carrying this variant had a shorter duration of treatment.

2024-02-01·Molecular Neurobiology

Identification of Key Genes and Immunological Features Associated with Copper Metabolism in Parkinson’s Disease by Bioinformatics Analysis

Article

作者: Zhang, Haofuzi ; Hao, Lu ; Jiang, Xiaofan ; Nagai, Jun

To explore diagnostic genes associated with cuproptosis in Parkinson's disease (PD) and to characterize immune cell infiltration by comprehensive bioinformatics analysis, three PD datasets were downloaded from the GEO database, two of which were merged and preprocessed as the internal training set and the remaining one as the external validation set. Based on the internal training set, differential analysis was performed to obtain differentially expressed genes (DEGs), and weighted gene co-expression network analysis (WGCNA) was conducted to obtain significant module genes. The genes obtained here were intersected to form the intersecting genes. The intersecting genes obtained from DEGs and WGCNA were intersected with cuproptosis-related genes (CRGs) to generate cuproptosis-related disease signature genes, and functional enrichment analysis was performed on Disease Ontology (DO), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, LASSO analysis of the cuproptosis-related disease signature genes was performed to identify key genes and construct a diagnostic and predictive model. Then, single sample gene set enrichment analysis (ssGSEA) was performed on the internal training set to further analyze the correlation between key genes and immune cells. Lastly, the results were validated using an external validation set. A total of 405 DEGs were obtained by differential analysis, and 6 gene modules were identified by WGCNA analysis. The genes in the most significant modules were intersected with the DEGs to obtain 21 intersecting genes. The functions of the intersecting genes were mainly enriched in neurotransmitter transport, GABA-ergic synapse, synaptic vesicle cycle, serotonergic synapse, phenylalanine metabolism, tyrosine metabolism, tryptophan metabolism, etc. Subsequently, the intersecting genes were intersected with CRGs, and LASSO regression analysis was performed to screen 3 key cuproptosis-related disease signature genes, namely, SLC18A2, SLC6A3, and SV2C. The calibration curve of the nomogram model constructed based on these 3 key genes to predict PD showed good agreement, with a C-index of 0.944 and an area under the ROC (AUC) of 0.944 (0.833-1.000). It was also validated by the external dataset that the model constructed with these 3 key genes had good diagnostic and predictive power for PD. The ssGSEA analysis revealed that neutrophils might be the potential core immune cells and that SLC18A2, SLC6A3, and SV2C were significantly negatively correlated with neutrophils, which was also verified in the validation set. PD diagnosis and prediction model based on CRGs (SLC18A2, SLC6A3, and SV2C) has good diagnostic and predictive performance and could be a useful tool in the diagnosis of PD.