| Annotated protein: | Glutamate receptor ionotropic, NMDA 3A (GluN3A) (Glutamate receptor chi-1) (N-methyl-D-aspartate receptor) (N-methyl-D-aspartate receptor subtype 3A) (NMDAR3A) (NR3A) (NMDAR-L) (NMDAR-L1). Gene symbol: GRIN3A. Taxonomy: Rattus norvegicus (Rat). Uniprot ID: Q9R1M7 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ GRIN3A |
| Ontology domain: | Cellular Component |
| SynGO term: | integral component of postsynaptic density membrane (GO:0099061) |
| Synapse type(s): | hippocampus, glutamatergic |
| Annotated paper: | Perez-Otano I, et al. "Endocytosis and synaptic removal of NR3A-containing NMDA receptors by PACSIN1/syndapin1" Nat Neurosci. 2006 May;9(5):611-21 PMID:16617342 |
| Figure(s): | Fig.1, 2, 3, 8 |
| Annotation description: | Fig.1: "NMDARs containing NR3A subunits are inefficiently targeted to synapses and reside in intracellular compartments" - "As expected, all NMDAR subunits were enriched in synaptic plasma membranes (SPMs) (Fig. 1e,f). However, within SPM subfractions, NR3A was present primarily in the Triton-soluble and PSDI fractions, whereas NR1 and NR2 were more abundant in the highly detergent-insoluble fractions PSDII and PSDIII (Fig. 1e,f), which correspond to the 'core' of the PSD" Fig.2: "NR3A localizes to extrasynaptic and perisynaptic membrane domains" - " At asymmetric synapses, NR3A labeling was preferentially observed at perisynaptic (less than 0.1 μm away from the PSD) or extrasynaptic (more than 0.1 μm away from the PSD) domains of the plasma membrane (Fig. 2d-f). A quantitative analysis revealed that NR3A was most concentrated at the lateral margin of the PSD, within 120 nm of the edge of the synaptic junction, but a fraction of membrane-associated particles was present at the PSD (Fig. 2g,h)." Fig.3: "Ultrastructural localization of NR3A at CA1 hippocampal synapses of adult rat using postembedding immunogold labeling" - "As with the pre-embedding methods, NR3A was found at synaptic junctions but was preferentially distributed peri- and extrasynaptically (Fig. 3a-d)" Fig.8: "Within dendritic spines, gold particles [for PACSIN1] were found at synaptic and perisynaptic sites, along the extrasynaptic plasma membrane, and associated with intracellular vesicles in lateral domains of the PSD (Fig. 8a). Double-labeling showed NR3A and PACSIN1 immunoparticles colocalizing at the same synaptic specialization (Fig. 8a)." Note: with perisynaptic the authors mean attached to the lateral side of the PSD. - GRIN3A seems to be a flexible consituent of the PSD that anchors at a different locations that other NMDARs. Some synapses show GRIN3A inside the PSD. This finding is inline with reports that show that GRIN3A-containing NMDARs move into the synapse stimulus dependently (see PMID:24183704). I annotate against the most specific term 'integral component of postsynaptic density membrane (GO:0099061)', also taking into account the hierarchical structure of the ontology (the term 'integral component of postsynaptic density membrane (GO:0099061)' implies presence in the 'integral component of postsynaptic membrane (GO:0099055)'). - Based on the known transmembrane topology of the protein, the "integral component of ... membrane" term was chosen. |
| Evidence tracking, Biological System: | Intact tissue |
| Evidence tracking, Protein Targeting: | Antibody (detection) |
| Evidence tracking, Experiment Assay: | Electron Microscopy |
| 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 |
| Additional literature: | GRIN3A moves into the PSD upon cocaine exposure (ePhys) @ PMID:24183704 |
| SynGO annotation ID: | 2659 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |