| Annotated protein: | Alpha-soluble NSF attachment protein (SNAP-alpha) (N-ethylmaleimide-sensitive factor attachment protein alpha). Gene symbol: NAPA. Taxonomy: Mus musculus (Mouse). Uniprot ID: Q9DB05 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ NAPA |
| Ontology domain: | Biological Process |
| SynGO term: | regulation of synaptic vesicle priming (GO:0010807) |
| Synapse type(s): | hippocampus, glutamatergic brain |
| Annotated paper: | Burgalossi A, et al. "SNARE protein recycling by alphaSNAP and betaSNAP supports synaptic vesicle priming" Neuron. 2010 Nov 4;68(3):473-87 PMID:21040848 |
| Figure(s): | S5, Fig.4-8 |
| Annotation description: | Alpha-SNAP supports SV priming by determining the availability of free SNARE components, particularly during phases of high synaptic activity. Alpha-SNAP KO mice are embryonically lethal (probably due to its function in other cellular membrane trafficking processes) and couldn't be used in the study. Therefore a hypomorph mutant (HYH) was used that results in a 50% reduction in alpha-SNAP protein levels. Synaptic transmission in autaptic hippocampal neuron cultures was unaffected in this mutant (Fig.S5A-E). Beta-SNAP KO mice were generated in this study. Synaptic transmission in autaptic hippocampal neuron cultures was unaffected in beta-SNAP KO mice (Fig.S6). Therefore, in the study a Beta-SNAP KO / HYH-double mutant was used since the single mutants did not exhibit any phenotypes, indicating that alpha- and betaSNAP have largely redundant functions. Double mutant mice exhibited a 70% reduction in combined alpha/beta-SNAP protein levels in brain homogenates (Fig.4A), an increase in assembled SNARE complexes (Fig.4B) due to a defect in SNARE-complex disassembly, and a small (~25%) reduction in the basal RRP size measured by hypertonic sucrose and high-frequency stimulation, with no changes in the EPSC size (Fig. 4C-F;Fig. 5A-C). 40 Hz and 100 Hz stimulation and calcimycin treatment revealed a strong perturbation in RRP refilling in double mutant neurons during/after high activity and elevated calcium (Fig. 5D-F, 6E-H). Overexpression of alpha-SNAP in double mutant neurons rescued the phenotype (Fig.7). Exogenous glutamate application was not changed in the double mutant before or after 100 Hz stimulation, indicating a selective presynaptic effect (Fig.8). SNARE-binding assays demonstrate that alpha- and beta-SNAP do not differ in their ability to be incorporated in the 20S complex composed of the SNARE-complex, SNAPs and NSF (Fig.S2E), indicating that they do not have different interaction partners in the synapse and probably have largely redundant functions. |
| Evidence tracking, Biological System: | Intact tissue Cultured neurons |
| Evidence tracking, Protein Targeting: | Genetic transformation (eg; knockout, knockin, mutations) Antibody (detection) |
| Evidence tracking, Experiment Assay: | Whole-cell patch clamp Western blot IP + WB/MSMS |
| Annotator(s): | Noa Lipstein (ORCID:0000-0002-0755-5899) Cordelia Imig (ORCID:0000-0001-7351-8706) Vincent O'connor (ORCID:0000-0003-3185-5709) Nils Brose (ORCID:0000-0003-0938-8534) |
| Lab: | Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany |
| SynGO annotation ID: | 716 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |