| Annotated protein: | Voltage-dependent calcium channel gamma-3 subunit (Neuronal voltage-gated calcium channel gamma-3 subunit) (Transmembrane AMPAR regulatory protein gamma-3) (TARP gamma-3). Gene symbol: CACNG3. Taxonomy: Mus musculus (Mouse). Uniprot ID: Q9JJV5 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ CACNG3 |
| Ontology domain: | Biological Process |
| SynGO term: | neurotransmitter receptor localization to postsynaptic specialization membrane (GO:0099645) |
| Synapse type(s): | cerebellum, glutamatergic |
| Annotated paper: | Menuz K, et al. "TARP redundancy is critical for maintaining AMPA receptor function" J Neurosci. 2008 Aug 27;28(35):8740-6 PMID:18753375 |
| Figure(s): | Figures 3, 4 |
| Annotation description: | In cerebellar Golgi cells, TARP γ-3 is "functionally redundant" with TARP γ-2. Together, they control the composition, abundance, and EPSC decay kinetics of synaptic AMPARs. Fig. 1, Table 1: "γ-2,3-/- mice fail to thrive" The majority of them die by P14, they are smaller and displayed more severe ataxia compared to γ-2 KO, "That the loss of γ-3 exaggerates the γ-2 behavioral phenotype suggests that these two TARPs may serve redundant functions." Fig. 3: "Cerebellar AMPA receptor protein expression in γ-2 and γ-3 knock-outs." GluR2/3 levels were unaffected in γ-3 KO, were reduced by 30% in γ-2 KO, and by 70% in γ-2/3 KO mice. "This synergistic reduction in GluA2/3 levels in the γ-2,3 mice implies a functional redundancy for these two closely related TARPs." AMPAR expression and function was unaffected in the forebrain and hippocampus of γ-2, γ-3, or γ-2/3 KO mice (Fig. 2). Fig. 4: "A single TARP family member is sufficient to preserve synaptic AMPA receptors." Golgi cell synaptic AMPAR-mediated transmission was quantified by stimulating parallel fibers. "Double KO mice had a nearly 90% reduction of AMPA/NMDA, whereas no change was seen in either single knock-out (Fig. 4A)." There was no change in the PPR, consistent with the loss of postsynaptic receptors (Fig. 4B). Analysis of Golgi cell mEPSC found no change in single KO mice, but a 90% decrease in mEPSC frequency and significant reduction in amplitude in DKO mice (Fig. 4C,D), suggesting "an equal loss of AMPARs from all synapses." Fig. 5: "Loss of TARPs affects AMPA receptor subunit composition." Native AMPAR require GluA2 to generate a linear I-V relationship, which was observed in WT and single KO mice. In double KO mice, I-V relationships of synaptic AMPAR-mediated currents were inwardly rectifying (Fig. 5B), indicating these synapses "contain a mixed population of GluA2-containing and GluA2-lacking AMPAR." |
| Evidence tracking, Biological System: | Intact tissue |
| Evidence tracking, Protein Targeting: | Genetic transformation (eg; knockout, knockin, mutations) |
| Evidence tracking, Experiment Assay: | 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 |
| Additional literature: | Fig. 1: Synaptic TARP γ-3 is stable at the cell surface during AMPA-induced receptor internalization (1C-D). AMPA or high K+ treatment reduced surface levels of TARP γ-3/AMPAR complexes (Fig. 1E-H). High K+-induced dissociation was sensitive to CNQX, "indicating that the release of endogenous glutamate disrupts the association of AMPARs with TARP γ-3." (cultured cortical neurons) Fig. 2: "Agonists binding dissociates AMPARs from TARPs." TARP γ-3 complexes immunoprecipitated from cerebral cortical membrane fractions using anti-TARP γ-3 or anti-GluA2/3 antibodies were treated with glutamate receptor agonists and antagonists. Bound proteins were examined by western blotting. 22/2/2018 Pim - Fig.1: "We next asked whether TARPs undergo activity-dependent endocytosis along with AMPA receptors. Neuronal activity was blocked by tetrodotoxin (2 μM), and protein internalization was monitored with a biotinylation assay (1). Endocytosis of AMPA receptors but not N-methyl-D-aspartate (NMDA) receptors was accelerated by treating cultures with AMPA (Fig. 1, C and D) (1, 3, 4). In contrast to AMPA receptors, stargazin and γ-3 turned over very slowly at the plasma membrane and their endocytosis was not influenced by AMPA (Fig. 1, C and D)." @ PMID:15001777 |
| SynGO annotation ID: | 2724 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |