| Annotated protein: | MAM domain-containing glycosylphosphatidylinositol anchor protein 1 (Ig6M). Gene symbol: MDGA1. Taxonomy: Rattus norvegicus (Rat). Uniprot ID: P85171 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ MDGA1 |
| Ontology domain: | Biological Process |
| SynGO term: | regulation of synapse maturation (GO:0090128) |
| Synapse type(s): | hippocampus, glutamatergic |
| Annotated paper: | Toledo A, et al. "MDGAs are fast-diffusing molecules that delay excitatory synapse development by altering neuroligin behavior" Elife. 2022 May 9;11:e75233 PMID:35532105 |
| Figure(s): | Figure 8 |
| Annotation description: | Figure 8: authors designed new DNA vectors based on the CRISPR/Cas9 strategy to achieve single-cell knock-out of MDGA1 or MDGA2 in dissociated neurons. At DIV10, an almost doubling in the number of PSD-95 (DLG4) puncta per unit dendrite length without a change in PSD-95 area, was observed in rat hippocampal neurons expressing gRNAs to MDGA1 or MDGA2 relatively to control gRNA (Figure 8A-C). However, MDGAs knock-out has no effect on synaptic density in DIV 14 neurons (Figure 8, figure supplement 3). Authors conclude that both MDGA1 and MDGA2 mainly impair excitatory post-synaptic assembly in the early phase of synaptogenesis. Author summary; "We demonstrate that both MDGA1 and MDGA2 (Figure 1, 2) are essentially non-synaptically enriched molecules that exhibit fast diffusion in the dendritic membrane (Figure 3, 4). Moreover, the knock-down of MDGAs selectively increases excitatory synapse density (Figure 8) and as a consequence reduces the surface mobility of both NLGN1 (Figure 5, 6) and AMPARs (Figure 7), increases AMPAR-mediated mEPSC frequency and evoked EPSC amplitude (Figure 9), as well as NLGN1 phosphosignaling (Figure 6). Thus, by shielding a fraction of NLGN1 from binding to pre-synaptic NRXNs, MDGAs negatively regulates NLGN function in excitatory synaptic differentiation (Figure 10)." |
| Evidence tracking, Biological System: | Cultured neurons |
| Evidence tracking, Protein Targeting: | Genetic transformation (eg; knockout, knockin, mutations) |
| Evidence tracking, Experiment Assay: | Confocal |
| Annotator(s): | Frank Koopmans (ORCID:0000-0002-4973-5732) 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: | 4928 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |