| Annotated protein: | Synaptotagmin-3 (Synaptotagmin III) (SytIII). Gene symbol: SYT3. Taxonomy: Mus musculus (Mouse). Uniprot ID: O35681 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ SYT3 |
| Ontology domain: | Biological Process |
| SynGO term: | regulation of postsynaptic membrane neurotransmitter receptor levels (GO:0099072) |
| Synapse type(s): | hippocampus |
| Annotated paper: | Awasthi A, et al. "Synaptotagmin-3 drives AMPA receptor endocytosis, depression of synapse strength, and forgetting" Science. 2019 Jan 4;363(6422):eaav1483 PMID:30545844 |
| Figure(s): | Figure 2 and 3 |
| Annotation description: | Figure 2E: Recombinant Syt3 pulled down GluA2 but not other receptor subunits and also pulled down the endocytic proteins AP-2 and BRAG2; two proteins implicated in receptor endocytosis. Figure 2G: Syt3 bound GluA2 in a calcium-dependent manner and bound AP-2 and BRAG2 in the absence of calcium, and at concentrations up to 10 μM in the case of AP2. Figure 3H: The nine-amino acid 3Y tail of GluA2 is important for receptor internalization. Incubation of brain lysates with 1 μM Tat-GluA2-3Y peptide disrupts Syt3:GluA2 binding indicating that SYT3 might be interacting with GluA2 via the receptor internalization region. Figure 3A-C: Overexpression of GFP-Syt3 increases internalization of GluA1 and GluA2, whereas Syt3 knockdown or expression of a calcium-binding-deficient mutant of Syt3 abolishes stimulation-induced internalization of receptors. Figure S4: Validation of Syt3 short hairpin RNA (shRNA) knockdown used in the aforementioned assay. Figure 3D-E and S4G: Syt3 knockout neurons yield similar results; GluA2 receptors are internalized in response to AMPA and NMDA stimulation in wild-type neurons but not in Syt3 knockout neurons or in wild-type neurons treated with the Tat-GluA2-3Y peptide. |
| Evidence tracking, Biological System: | Cultured neurons |
| Evidence tracking, Protein Targeting: | Genetic transformation (eg; knockout, knockin, mutations) RNAi / shRNA Antibody (detection) |
| Evidence tracking, Experiment Assay: | Confocal IP + WB/MSMS |
| Annotator(s): | Dnyanada Sahasrabudhe (ORCID:0000-0003-2916-7616) Guus Smit (ORCID:0000-0002-2286-1587) Matthijs Verhage (ORCID:0000-0002-2514-0216) |
| Lab: | Department of Functional Genomics, Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands |
| SynGO annotation ID: | 4543 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |