ArticleThe Journal of biological chemistry2013
Macromolecular composition dictates receptor and G protein selectivity of regulator of G protein signaling (RGS) 7 and 9-2 protein complexes in living cells.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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44 citing papers in PubMed, 59 citations in OpenAlex.
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- Receptor-dependent influence of R7 RGS proteins on neuronal GIRK channel signaling dynamics.Progress in neurobiology · 2024Article
- Rules and mechanisms governing G protein coupling selectivity of GPCRs.Cell reports · 2023Article
- Fine-tuning GPCR-mediated neuromodulation by biasing signaling through different G protein subunits.Molecular cell · 2023Article
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- Altered Intracellular Signaling Associated with Dopamine D2 Receptor in the Prefrontal Cortex in Wistar Kyoto Rats.International journal of molecular sciences · 2023Article
- Neuronal G protein-gated KAmerican journal of physiology. Cell physiology · 2022Review
- OZITX, a pertussis toxin-like protein for occluding inhibitory G protein signalling including GαCommunications biology · 2022Article
- Structure of the class C orphan GPCR GPR158 in complex with RGS7-Gβ5.Nature communications · 2021Article
- Identification of Potential Modulators of the RGS7/Gβ5/R7BP Complex.SLAS discovery : advancing life sciences R & D · 2021Article
- Residue-level determinants of RGS R4 subfamily GAP activity and specificity towards the GCellular and molecular life sciences : CMLS · 2021Article
- Diversity of the Gβγ complexes defines spatial and temporal bias of GPCR signaling.Cell systems · 2021Article
- Regulators of G Protein Signaling in Analgesia and Addiction.Molecular pharmacology · 2020Review
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- GPCR-dependent biasing of GIRK channel signaling dynamics by RGS6 in mouse sinoatrial nodal cells.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Probing the mutational landscape of regulators of G protein signaling proteins in cancer.Science signaling · 2020Article
- The in vivo specificity of synaptic Gβ and Gγ subunits to the αScientific reports · 2019Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Regulator of G protein signaling (RGS) proteins play essential roles in the regulation of signaling via G protein-coupled receptors (GPCRs). With hundreds of GPCRs and dozens of G proteins, it is important to understand how RGS regulates selective GPCR-G protein signaling. In neurons of the striatum, two RGS proteins, RGS7 and RGS9-2, regulate signaling by μ-opioid receptor (MOR) and dopamine D2 receptor (D2R) and are implicated in drug addiction, movement disorders, and nociception. Both proteins form trimeric complexes with the atypical G protein β subunit Gβ5 and a membrane anchor, R7BP. In this study, we examined GTPase-accelerating protein (GAP) activity as well as Gα and GPCR selectivity of RGS7 and RGS9-2 complexes in live cells using a bioluminescence resonance energy transfer-based assay that monitors dissociation of G protein subunits. We showed that RGS9-2/Gβ5 regulated both Gi and Go with a bias toward Go, but RGS7/Gβ5 could serve as a GAP only for Go. Interestingly, R7BP enhanced GAP activity of RGS7 and RGS9-2 toward Go and Gi and enabled RGS7 to regulate Gi signaling. Neither RGS7 nor RGS9-2 had any activity toward Gz, Gs, or Gq in the absence or presence of R7BP. We also observed no effect of GPCRs (MOR and D2R) on the G protein bias of R7 RGS proteins. However, the GAP activity of RGS9-2 showed a strong receptor preference for D2R over MOR. Finally, RGS7 displayed an four times greater GAP activity relative to RGS9-2. These findings illustrate the principles involved in establishing G protein and GPCR selectivity of striatal RGS proteins.
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