| Annotated protein: | Voltage-dependent calcium channel gamma-7 subunit (Neuronal voltage-gated calcium channel gamma-7 subunit) (Transmembrane AMPAR regulatory protein gamma-7) (TARP gamma-7). Gene symbol: CACNG7. Taxonomy: Mus musculus (Mouse). Uniprot ID: P62956 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ CACNG7 |
| Ontology domain: | Biological Process |
| SynGO term: | neurotransmitter receptor localization to postsynaptic specialization membrane (GO:0099645) |
| Synapse type(s): | cerebellum, glutamatergic |
| Annotated paper: | Studniarczyk D, et al. "TARP gamma-7 selectively enhances synaptic expression of calcium-permeable AMPARs" Nat Neurosci. 2013 Sep;16(9):1266-74 PMID:23872597 |
| Figure(s): | Figures 4, 5, 6, 7; Supplementary Tables 1-3, |
| Annotation description: | TARP γ-7 regulates the synaptic expression of calcium-permeable (CP)-AMPARs in granule cells. Fig. 3: "CP-AMPARs are successfully trafficked to the cell surface in stg/stg cerebellar granule cells." γ-2 is not required for synaptic expression of CP-AMPARs. Fig. 4, Supplementary Tables 1 and 2: "The presence of γ-7 determines the surface expression of CI-AMPARs in WT and stg/stg cerebellar granule cells." shRNA-knockdown of γ-7 in WT granule cells increased the mean whole-cell AMPA-evoked current; the I-V relationships remained linear (Fig. 4a-d). Knockdown of γ-7 in stg/stg cells rescued AMPAR expression (large whole-cell currents); the I-V relationships showed little rectification (Fig. 4e-h). Conclusion: "In granule cells, γ-7 seems to suppress CI-AMPAR function." Fig. 5: "Single- and double-knockdown experiments suggest a role of γ-7 in the regulation of synaptic AMPARs." mEPSCs are detected in WT granule cells following knockdown of γ-7. Granule cells in stg/stg mice lack synaptic currents despite the presence of γ-7. Conclusion: "CI-AMPARs can reach the synapse in the absence of γ-7." Knockdown of both GluA2 and γ-7 in WT granule cells produced mEPSCs with reduced amplitudes and underlying synaptic channel conductances (compared with GluA2-knockdown, Fig. 5b). The mEPSCs in GluA2- and γ-7-knockdown cells remained strongly rectifying (Fig. 2b and Supplementary Table 3); suggesting that synaptic CP-AMPARs "are TARPless after knockdown of γ-7" as well as "cooperative action of the two TARPs, with γ-2 being unable to associate with synaptic receptors in the absence of γ-7." stg/stg granule cells where both GluA2 and γ-7 were knocked down showed strongly rectifying mEPSCs. Conclusion: "Thus, although the presence of γ-7 does not seem to be necessary for CP-AMPAR delivery to the synapse, by suppressing the synaptic targeting of CI-AMPARs while permitting delivery of their calcium-permeable counterparts, TARP γ-7 selectively favors the synaptic targeting of CP-AMPARs." Fig. 6: "AMPAR subunits GluA2 and GluA4 coimmunoprecipitate with TARP γ-7 in cerebellar lysates from both WT and stg/stg mice." γ-7 also immunoprecipitated with γ-2 from WT but not stg/stg cerebellar extracts. "These results suggest that individual receptors can bind both γ-2 and γ-7 within the same assembly. Fig. 7: "Overexpression of γ-7 in cerebellar granule cells causes a switch from CI-AMPARs to CP-AMPARs." Overexpression of γ-7 in WT granule cells resulted in AMPAR-mediated currents that showed strong inward rectification as well as elevated amplitudes (Fig. 7a, Supplementary Tables 1 and 2). Overexpression of γ-2 also increased the whole-cell currents, however, the cells retained a linear I-V relationship similar to WT cells (Fig. 7b-d). Overexpression of γ-7 also increased the amplitudes and inward rectification of mEPSCs (Fig. 7e, f). "Taken together, our data indicate that increased expression of γ-7 increases the prevalence of CP-AMPARs at synaptic and extrasynaptic sites." "This presumably reflects the fact that granule cells from WT mice express γ-2 and is in keeping with our finding that the presence of both γ-2 and γ-7 is necessary and sufficient for synaptic CP-AMPARs to be TARPed in granule cells." |
| Evidence tracking, Biological System: | Cultured neurons |
| Evidence tracking, Protein Targeting: | Genetic transformation (eg; knockout, knockin, mutations) RNAi / shRNA Over-expression |
| Evidence tracking, Experiment Assay: | 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 |
| Additional literature: | Figure 2, 3, 6, 7, 8: TARP γ-7 enhances peak currents from homomeric GluA1 and GluA2-AMPARs (Fig. 2B, 3). Co-expression of TARP γ-7 with GluR1iQ, GluR2iQ, or GluR2iR in HEK cells enhanced glutamate-evoked currents. TARP γ-7 attenuated the peak current and potentiate the steady-state currents in cells expressing GluA3-AMPARs (Fig. 3). Peak and steady state currents from GluA4-AMPARs were unaffected by TARP γ-7 (Fig. 3). Fig.7: TARP γ-7 regulates GluA1/2- and GluA2/3-AMPARs in a similar manner. Coexpression γ-7 with GluA1/2 augmented the peak and steady-state currents (with or without CTZ) from these receptors compared to either GluA1 or GluA2 alone Peak and steady-state currents were recorded from HEK cells transfected with TARP γ-7 and either GluR1iQ/GluR2iR or GluR2iR/GluR3iQ (the major types of AMPARs found in cortical and hippocampal neurons) following glutamate application. TARP γ-7 imparts an unusual effect on the desensitization of GluA1 and GluA2 AMPARs which is marked by an initial decay in current from the peak response followed by a slow increase in current to steady state (Fig. 2B, . @ PMID:18817736 TARP γ-7 is an integral membrane protein belonging to the type II family of TARPs. Unlike type I TARPs, which potentiate all subunit compositions of AMPARs, type II TARPs display subunit-specific regulation of AMPARs. Fig. 1: "AMPA receptor-mediated synaptic currents of Purkinje cells in stg/γ-7 double KO cerebella were significantly reduced." Climbing fiber-mediated EPSCs from WT, γ-7-KO, stargazer (stg, lacks TARP γ-2), and stg/γ-7KO (dKO) mice, P31-58. Fig. 2: "Synaptic and extrasynaptic AMPARs in stellate cells from stg/γ-7 double KO mice are not significantly reduced in comparison with stargazer mice alone." mEPSCs and evoked EPSCs (kainate or glutamate) from WT, stg, and dKO cerebellar stellate cells. Fig. 3: "TARP γ-7 has no apparent effect on AMPAR currents in dissociated cerebellar granule cells." No significant difference in the amplitude, frequency or decay kinetics in CGNs from γ-7 KO mice compared to controls. sNMDAR-mediated events and glutamate-evoked currents were also not affected in γ-7 KO CGNs. Fig. 4: "AMPA receptor-mediated synaptic currents were significantly reduced in Purkinje cell-specific γ-2/γ-7-double KO mice." While loss of γ-7 alone had little effect on climbing fiber (cf) responses in Purkinje neurons (PCs), the additional loss of γ-2 abolished cf responses. γ-2 PC KO; γ-7 KO mice: Germ-line γ-7 KO mouse (no behavioral abnormalities) was crossed to a conditional γ-2 KO mouse in which Cre is selectively expressed in PCs under the control of the L7 promoter (Pcp2-cre). Fig. 6: Motor behaviors are impaired in γ-7 KO mice also lacking γ-2 in Purkinje cells. Loss of γ-2 in PCs with γ-7 severely disrupted motor behavior. "γ-7 is capable of supporting a component of excitatory transmission in PCs, sufficient to maintain essentially normal motor behavior, in the absence of γ-2" Supplementary Fig. S1, S3: Validation of γ-7 KO mouse. @ PMID:25583485 |
| SynGO annotation ID: | 2855 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |