ArticleProceedings of the National Academy of Sciences of the United States of America2012
GIRK channel modulation by assembly with allosterically regulated RGS proteins.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 43 citations in OpenAlex.
- RGS6 regulates Kappa opioid receptor-mediated antinociceptive behaviors.Neuropharmacology · 2026Article
- Emerging modes of regulation of neuromodulatory G protein-coupled receptors.Trends in neurosciences · 2024Review
- Dissecting the molecular basis for the modulation of neurotransmitter GPCR signaling by GINIP.Structure (London, England : 1993) · 2024Article
- Leukocyte differential gene expression prognostic value for high versus low seizure frequency in temporal lobe epilepsy.BMC neurology · 2024Article
- Dissecting the molecular basis for the modulation of neurotransmitter GPCR signaling by GINIP.bioRxiv : the preprint server for biology · 2023Article
- The Relevance of GIRK Channels in Heart Function.Membranes · 2022Review
- A Novel Tree Shrew Model of Chronic Experimental Autoimmune Uveitis and Its Disruptive Application.Frontiers in immunology · 2022Article
- GABACurrent topics in behavioral neurosciences · 2022Review
- Regulators of G Protein Signaling in Analgesia and Addiction.Molecular pharmacology · 2020Review
- Regulator of G-Protein Signaling (RGS) Protein Modulation of Opioid Receptor Signaling as a Potential Target for Pain Management.Frontiers in molecular neuroscience · 2020Review
- RGS4 Maintains Chronic Pain Symptoms in Rodent Models.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Structural organization of a major neuronal G protein regulator, the RGS7-Gβ5-R7BP complex.eLife · 2018Article
- Inhibitory Signaling to Ion Channels in Hippocampal Neurons Is Differentially Regulated by Alternative Macromolecular Complexes of RGS7.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Regulators of G-Protein Signaling (RGS) Proteins Promote Receptor Coupling to G-Protein-Coupled Inwardly Rectifying Potassium (GIRK) Channels.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- A High-Throughput Time-Resolved Fluorescence Energy Transfer Assay to Screen for Modulators of RGS7/Gβ5/R7BP Complex.Assay and drug development technologies · 2018Article
- Regulator of G protein signaling-12 modulates the dopamine transporter in ventral striatum and locomotor responses to psychostimulants.Journal of psychopharmacology (Oxford, England) · 2018Article
- Regulation of neurite morphogenesis by interaction between R7 regulator of G protein signaling complexes and G protein subunit GαThe Journal of biological chemistry · 2017Article
- Relationship in Pacemaker Neurons Between the Long-Term Correlations of Membrane Voltage Fluctuations and the Corresponding Duration of the Inter-Spike Interval.The Journal of membrane biology · 2017Article
- Article
- KCTD Hetero-oligomers Confer Unique Kinetic Properties on Hippocampal GABAB Receptor-Induced K+ Currents.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
G-protein-activated inward-rectifying K(+) (GIRK) channels hyperpolarize neurons to inhibit synaptic transmission throughout the nervous system. By accelerating G-protein deactivation kinetics, the regulator of G-protein signaling (RGS) protein family modulates the timing of GIRK activity. Despite many investigations, whether RGS proteins modulate GIRK activity in neurons by mechanisms involving kinetic coupling, collision coupling, or macromolecular complex formation has remained unknown. Here we show that GIRK modulation occurs by channel assembly with R7-RGS/Gβ5 complexes under allosteric control of R7 RGS-binding protein (R7BP). Elimination of R7BP occludes the Gβ5 subunit that interacts with GIRK channels. R7BP-bound R7-RGS/Gβ5 complexes and Gβγ dimers interact noncompetitively with the intracellular domain of GIRK channels to facilitate rapid activation and deactivation of GIRK currents. By disrupting this allosterically regulated assembly mechanism, R7BP ablation augments GIRK activity. This enhanced GIRK activity increases the drug effects of agonists acting at G-protein-coupled receptors that signal via GIRK channels, as indicated by greater antinociceptive effects of GABA(B) or μ-opioid receptor agonists. These findings show that GIRK current modulation in vivo requires channel assembly with allosterically regulated RGS protein complexes, which provide a target for modulating GIRK activity in neurological disorders in which these channels have crucial roles, including pain, epilepsy, Parkinson's disease and Down syndrome.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.