| Annotated protein: | Germ cell-specific gene 1-like protein (GSG1-like protein). Gene symbol: GSG1L. Taxonomy: Mus musculus (Mouse). Uniprot ID: D3Z7H4 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ GSG1L |
| Ontology domain: | Biological Process |
| SynGO term: | regulation of postsynaptic neurotransmitter receptor endocytosis (GO:0099149) |
| Synapse type(s): | hippocampus, glutamatergic Schaffer collateral synapse (CA3->CA1) |
| Annotated paper: | Gu X, et al. "GSG1L suppresses AMPA receptor-mediated synaptic transmission and uniquely modulates AMPA receptor kinetics in hippocampal neurons" Nat Commun. 2016 Mar 2;7:10873 PMID:26932439 |
| Figure(s): | Figures 1, 2, 5; and supplementary figures 4, 5, 7 |
| Annotation description: | GSG1L negatively regulates AMPAR abundance at synapses in hippocampal CA1 pyramidal neurons Fig. 1: "Overexpression of GSG1L in CA1 pyramidal neurons strongly reduced AMPA EPSCs." Cultured organotypic hippocampal slices were biolistically transfected with gold particles coated with plasmids expressing GSG1L fused or GSG1L-IRES-GFP. Simultaneous dual whole-cell voltage clamp recordings were made from a transfected CA1 pyramidal cell and a neighboring control cell to measure AMPA and NMDA excitatory postsynaptic currents (EPSCs). The amplitudes of AMPA EPSCs were reduced by ~80% in CA1 pyramidal cells transfected with GSG1L-GFP or GSG1L-IRES-GFP compared to neighboring control cells. NMDA EPSC amplitudes, PPR, and spine density were unaffected (Supplementary Fig. 2-3, Fig.1D). Neurons overexposing GSG1L also showed a strong reduction of m/sEPSC frequency and m/sEPSC amplitudes (Fig. 1E-F). Together these data show that "overexpression of GSG1L induced a loss of functional AMPARs at the majority of synapses (that is, strong decrease of m/sEPSC frequency) and a reduced amount of functional AMPARs at the remaining synapses (that is, significant decrease of m/sEPSC amplitude)" Fig. 2: "Overexpression of GSG1L impaired AMPAR trafficking to synaptic and extrasynaptic membranes." Molecular replacement assays in AMPAR triple conditional KO mice (Gria1-3f/f). Expression of Cre leads to a complete loss of AMPA EPSCs in neurons from Gria1-3f/f, which is rescued by expression of Cre with GluA1 (~75% rescue of AMPAR transmission, Supplementary Fig. 4A). Expression of GluA1 covalently linked to GSG1L (GluA1/GSG1L) with Cre only rescued ~20% of AMPA EPSCs suggesting GSG1L association with GluA1 "prevents the receptor trafficking to synapses" (Supplementary Fig. 4B and Fig. 2A). Overexpression of GSG1L decreased AMPAR-mediated, somatic outside-out patch currents by ~80% (Fig. 2C, measures AMPARs at somatic extrasynaptic membranes). Current-voltage (I/V) relationship analysis showed GluA2 content of somatic surface AMPARs was not affected (Fig. 2D). Immunolabeling of surface AMPARs in primary hippocampal neurons showed overexpression of GSG1L reduced surface GluA1 and GluA2 subunits (Fig. 2E and Supplementary Fig. 5), Fig. 5: "AMPA EPSCs and LTP were increased in CA1 pyramidal neurons in GSG1L KO rats" In cultured hippocampal neurons from GSG1L KO rats, immunolabelling of surface GluA1 and GluA2 AMPARs (sGluA1, sGluA2) was enhanced (Supplementary Fig. 7A-B). In CA1 pyramidal neurons from KO rats, the AMPA/NMDA EPSCs ratios and AMPAR-mediated mEPSC frequency were increased compared to control cells (Fig. 5A, C). There was no difference in mEPSC amplitude or PPR (Fig. 5B-C). Expression of GSG1L in CA1 pyramidal neurons in KO organotypic slice cultures strongly reduced AMPA EPSCs (Fig. 5d). In GSG1L KO neurons, endocytosis of sGluA1 was reduced (Fig. 5E) with no measurable effect on the recycling of internalized GluA1 (Supplementary Fig. 7C). Overexpressing GSG1L in cultured neurons enhanced the endocytosis of sGluA1 (Supplementary Fig. 7D). Authors mention "the strong reduction of sGluA1 led to little internalized GluA1 in GSG1L-overexpressing neurons, which prevented us from performing recycling assay in neurons overexpressing GSG1L." Fig. 4: Characterization and validation of Gsg1l knockout (KO) rats. |
| Evidence tracking, Biological System: | Intact tissue Cultured neurons Non-neuronal tissue |
| Evidence tracking, Protein Targeting: | Genetic transformation (eg; knockout, knockin, mutations) Over-expression Antibody (detection) |
| Evidence tracking, Experiment Assay: | Confocal Whole-cell patch clamp Electrophysiology (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 |
| SynGO annotation ID: | 2645 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |