| Annotated protein: | Voltage-dependent calcium channel gamma-2 subunit (Neuronal voltage-gated calcium channel gamma-2 subunit) (Stargazin) (Transmembrane AMPAR regulatory protein gamma-2) (TARP gamma-2). Gene symbol: CACNG2. Taxonomy: Mus musculus (Mouse). Uniprot ID: O88602 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ CACNG2 |
| Ontology domain: | Biological Process |
| SynGO term: | regulation of postsynaptic membrane neurotransmitter receptor levels (GO:0099072) |
| Synapse type(s): | hippocampus, glutamatergic cerebellum, glutamatergic Mossy fiber synapse (DG->CA3) |
| Annotated paper: | Chen L, et al. "Stargazin regulates synaptic targeting of AMPA receptors by two distinct mechanisms" Nature. 2000 Dec 21-28;408(6815):936-43 PMID:11140673 |
| Figure(s): | Figures 1, 4-7 |
| Annotation description: | Stargazin (TARP γ-2) facilitates the surface delivery and synaptic targeting of AMPARs through direct protein-protein interactions with the receptor and PSD-95 and SAP-97. The C-terminal PDZ domain of stargazin is required for the synaptic targeting but not surface delivery of AMPARs in cerebellar cells and hippocampal pyramidal cells. Fig 1: "Functional AMPARs are absent at stg/stg granule cell synapses in culture." Spontaneous AMPAR EPSCs are are essentially absent in stg/stg granule cells with EPSC amplitudes close to the threshold value (4pA, Fig. 1C) used to detect events and occurred at a frequency of 0.1Hz (compared to 1.7Hz in stg/+ cells). Immunostaining of cultured cerebellar cells from stg/stg mice had few synaptic GluR4 puncta (Fig 1G), which was also observed at mossy fibre synapses in the intact cerebellar glomeruli from these animals as well as a 10-fold decrease in synaptic GluA2/3 puncta (Fig. 2). Fig. 4: "Stargazin interacts with AMPARs and PDZ proteins" Stargazin interacts with GluA1, GluA2 and GluA4 in COS cells as well as PSD-95 and SAP-97. Deletion of the C-terminal, type I PDZ binding site (stargazinΔC) disrupted PSD-95 but not GluA4 binding (Fig. 4F). Co-expression of stargazin with PSD-95 and GluA4 redistributes the proteins to "patch-like cluters" (Fig. 4H). Fig. 5: "Surface AMPARs are absent in stg/stg granule cells." Fig. 6: "Stargazin rescues AMPAR responses in stg/stg granule cells" While stargazinΔC could rescue glutamate-evoked responses in stg/stg neurons, it failed to recover spontaneous AMPAR responses (Fig. 6A-D). Expression of stargazinΔC in wt neurons significantly reduced the amplitude and frequency of spontaneous synaptic AMPAR events. FIg. 7 "stargazinΔC downregulates hippocampal excitatory synapses" In cultured hippocampal neurons, stargazin-GFP puncta colocalized with endogenous GluA1 but not GAD 65. Expression of stargazinΔC-GFP, which showed a diffuse distribution in these neurons, significantly reduced the amplitude and frequency of AMPAR mEPSCs compared to untransfected cells. stargazinΔC-GFP had no effect on glutamate-induced currents. |
| Evidence tracking, Biological System: | Intact tissue Cultured neurons |
| Evidence tracking, Protein Targeting: | Genetic transformation (eg; knockout, knockin, mutations) Over-expression |
| Evidence tracking, Experiment Assay: | Electron Microscopy Confocal Whole-cell patch clamp Electrophysiology (generic) Western blot Protein-protein interaction (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: | 2502 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |