| Annotated protein: | Glutamate receptor ionotropic, delta-1 (GluD1) (GluR delta-1 subunit). Gene symbol: GRID1. Taxonomy: Mus musculus (Mouse). Uniprot ID: Q61627 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ GRID1 |
| Ontology domain: | Biological Process |
| SynGO term: | regulation of postsynapse organization (GO:0099175) |
| Synapse type(s): | hippocampus, glutamatergic cerebral cortex, glutamatergic |
| Annotated paper: | Gupta SC, et al. "Essential role of GluD1 in dendritic spine development and GluN2B to GluN2A NMDAR subunit switch in the cortex and hippocampus reveals ability of GluN2B inhibition in correcting hyperconnectivity" Neuropharmacology. 2015 Jun;93:274-84 PMID:25721396 |
| Figure(s): | Figures 1, 2, 3, 4 |
| Annotation description: | Glutamate delta-1 (GluD1) is an iGluRs that regulates spine development in the cortex and hippocampus. Fig. 1: "GluD1 KO mice exhibit impaired spine development and higher excitatory neurotransmission in the medial prefrontal cortex." No reduction in spine density between P14-P30 was observed in GluD1 KO pyramidal neurons (prelimbic cortex, layer II-III). Whole-cell recordings found a higher frequency of mEPSCs in GluD1 KO pyramidal neurons from prelimbic cortex, "consistent with the higher number of mushroom-like spines." No difference in the amplitude or decay of mEPSCs was observed, suggesting that while there are more mature synapses in GluD1 KO, they are not dissimilar in AMPA receptor function. Fig. 2: "Inhibition of GluN2B-containing receptors reverses the downreguated p-cofilin-p-LIMK1 signaling and higher spine density in GluD1 KO mice." Western blot analysis of synaptoneurosomes purified from WT and GluD1 KO mPFC showed abnormality in LIMK1-cofilin signaling in GluD1 KO samples (lower p-cofilin, p-LIMK). The ratio of GluN2A to GluN2B expression was significantly lower in GluD1 KO mice. Systemic administration of high-affinity GluN2B-selective inhibitor Ro-25-6981 was sufficient to normalize signaling and spine density in KO mice. Fig. 3: "The abnormalities in spine development and signaling are conserved between the hippocampus and mPFC in the GluD1 KO mice." Spine density in apical dendrites of CA1 hippocampal neurons remained unchanged from P14-P60 in GluD1 KO mice (compared to the significant reduction seen in WT mice). LIMK-cofilin signaling was also impaired as was the the ratio of expression of GluN2A/GluN2B. remained unchanged from P14 up to P60 Loss of GluD1 resulted in elevated Fig. 4: "Higher synaptic punctas in the mPFC and CA1 hippocampal area of GluD1 KO mice." The number of co-localized PSD95-synaptophysin puncta was elevated in both regions at P14 and P30 in GluD1 KO mice compared to WT. |
| Evidence tracking, Biological System: | Intact tissue |
| Evidence tracking, Protein Targeting: | Genetic transformation (eg; knockout, knockin, mutations) Antagonist / agonist Antibody (detection) |
| Evidence tracking, Experiment Assay: | Confocal Whole-cell patch clamp Electrophysiology (generic) Western blot Biochemical fractionation (generic) |
| Annotator(s): | Hana Goldschmidt (ORCID:0000-0002-5676-366X) Richard Huganir (ORCID:0000-0001-9783-5183) |
| Lab: | Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA and Kavli Neuroscience Discovery Institute, Johns Hopkins University, Baltimore, MD 21205, USA |
| Additional literature: | GluD1 induces inhibitory synapse formation in cultured cortical neurons via Cbln1 and Cbln2 @ PMID:22191730 |
| SynGO annotation ID: | 2694 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |