| Annotated protein: | MAM domain-containing glycosylphosphatidylinositol anchor protein 2 (MAM domain-containing protein 1). Gene symbol: MDGA2. Taxonomy: Mus musculus (Mouse). Uniprot ID: P60755 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ MDGA2 |
| Ontology domain: | Biological Process |
| SynGO term: | regulation of presynapse assembly (GO:1905606) |
| Synapse type(s): | hippocampus, glutamatergic hippocampus, GABAergic |
| Annotated paper: | Connor SA, et al. "Altered Cortical Dynamics and Cognitive Function upon Haploinsufficiency of the Autism-Linked Excitatory Synaptic Suppressor MDGA2" Neuron. 2016 Sep 7;91(5):1052-1068 PMID:27608760 |
| Figure(s): | Fig.1, 2, 3 |
| Annotation description: | Fig.1: "MDGA2 Inhibits the Synaptogenic Activity of NL1 and NL2 by Blocking Their Interaction with Nrx" - "In comparison with an unrelated negative control membrane protein HA-CD4, co-expression of HA-MDGA2 along with CFP-NL1 or CFP-NL2 significantly suppressed presynaptic induction by either NL1 or NL2 (Figures 1B-1E). In the same assay, HA-MDGA1 suppressed presynaptic induction by NL2, but not NL1, as expected (Pettem et al., 2013b)." - "Alternatively, MDGA2 might suppress synaptogenesis by inhibiting trans-synaptic interaction between NLs and presynaptic Nrxs. To test this idea, we performed a cell-based binding assay with a Myc-tagged soluble ectodomain of Nrx-1β fused to alkaline phosphatase (Myc-Nrx-AP). In comparison with HA-CD4 control, cells co-expressing HA-MDGA2 together with CFP-NL1 or CFP-NL2 showed significantly reduced binding of Myc-Nrx-AP (Figures 1F-1I). These data indicate that, similar to MDGA1, MDGA2 restricts presynaptic induction through postsynaptic interaction with NL and inhibition of NL interaction with Nrxs." Fig.2: "Overexpression of MDGA2 Suppresses Both Inhibitory and Excitatory Synapse Development" - "o assay this, we compared synapse density in cultured neurons transfected with either HA-MDGA2 or control V5-CD4 (Figures 2A-2D). Quantification of clusters of presynaptic vesicular GABA transporter (VGAT) apposed to gephyrin postsynaptic scaffolds revealed reduced density of inhibitory synapses. Excitatory synapse density was similarly suppressed as shown by reduced vesicular glutamate transporter (VGluT1)-positive PSD-95 clusters in neurons overexpressing HA-MDGA2. To determine if MDGA2 overexpression resulted in reduction of functional indicators of synapse density, we quantified miniature inhibitory and excitatory postsynaptic currents (mIPSCs and mEPSCs). Both mIPSC and mEPSC frequencies were significantly reduced in neurons overexpressing MDGA2 relative to control CD4, with no change in respective amplitudes (Figures 2E-2J). These data indicate that excess MDGA2 limits excitatory and inhibitory synapse development in cultured neurons." Fig.3: "Mdga2 Knockout Is Lethal and Haploinsufficiency Increases Excitatory Synapse Density" |
| Evidence tracking, Biological System: | Intact tissue Cultured neurons Non-neuronal tissue |
| Evidence tracking, Protein Targeting: | Genetic transformation (eg; knockout, knockin, mutations) Over-expression |
| Evidence tracking, Experiment Assay: | Confocal Whole-cell patch clamp |
| Annotator(s): | Pim van Nierop (ORCID:0000-0003-0593-3443) 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: | 2842 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |