ArticleThe Journal of biological chemistry2012
Regulator of G protein signaling 6 (RGS6) protein ensures coordination of motor movement by modulating GABAB receptor signaling.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 57 citations in OpenAlex.
- RGS6 regulates Kappa opioid receptor-mediated antinociceptive behaviors.Neuropharmacology · 2026Article
- A pediatric case of anti-GABAFrontiers in pediatrics · 2025Article
- Receptor-dependent influence of R7 RGS proteins on neuronal GIRK channel signaling dynamics.Progress in neurobiology · 2024Article
- Regulator of G protein signaling 6 (RGS6) in dopamine neurons promotes EtOH seeking, behavioral reward, and susceptibility to relapse.Psychopharmacology · 2024Article
- Direct modulation of G protein-gated inwardly rectifying potassium (GIRK) channels.Frontiers in physiology · 2024Review
- Regulator of G protein signaling protein 6 alleviates acute lung injury by inhibiting inflammation and promoting cell self-renewal in mice.Cellular & molecular biology letters · 2023Article
- RGS6 negatively regulates inhibitory G protein signaling in dopamine neurons and positively regulates binge-like alcohol consumption in mice.British journal of pharmacology · 2023Article
- Neuronal G protein-gated KAmerican journal of physiology. Cell physiology · 2022Review
- RGS6 suppresses TGF-β-induced epithelial-mesenchymal transition in non-small cell lung cancers via a novel mechanism dependent on its interaction with SMAD4.Cell death & disease · 2022Article
- Stereological estimations and neurochemical characterization of neurons expressing GABAA and GABAB receptors in the rat pedunculopontine and laterodorsal tegmental nuclei.Brain structure & function · 2022Article
- Mechanisms and Regulation of Neuronal GABACurrent topics in behavioral neurosciences · 2022Review
- Hepatic Regulator of G Protein Signaling 6 (RGS6) drives non-alcoholic fatty liver disease by promoting oxidative stress and ATM-dependent cell death.Redox biology · 2021Article
- RGS Proteins as Critical Regulators of Motor Function and Their Implications in Parkinson's Disease.Molecular pharmacology · 2020Review
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- Review
- Age-dependent nigral dopaminergic neurodegeneration and α-synuclein accumulation in RGS6-deficient mice.JCI insight · 2019Article
- 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
- Neonatal brain injury causes cerebellar learning deficits and Purkinje cell dysfunction.Nature communications · 2018Article
- Diversity of structure and function of GABAProceedings of the Japan Academy. Series B, Physical and biological sciences · 2018Review
- Essentiality of Regulator of G Protein Signaling 6 and Oxidized CaJournal of the American Heart Association · 2017Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
γ-Aminobutyric acid (GABA) release from inhibitory interneurons located within the cerebellar cortex limits the extent of neuronal excitation in part through activation of metabotropic GABA(B) receptors. Stimulation of these receptors triggers a number of downstream signaling events, including activation of GIRK channels by the Gβγ dimer resulting in membrane hyperpolarization and inhibition of neurotransmitter release from presynaptic sites. Here, we identify RGS6, a member of the R7 subfamily of RGS proteins, as a key regulator of GABA(B)R signaling in cerebellum. RGS6 is enriched in the granule cell layer of the cerebellum along with neuronal GIRK channel subunits 1 and 2 where RGS6 forms a complex with known binding partners Gβ(5) and R7BP. Mice lacking RGS6 exhibit abnormal gait and ataxia characterized by impaired rotarod performance improved by treatment with a GABA(B)R antagonist. RGS6(-/-) mice administered baclofen also showed exaggerated motor coordination deficits compared with their wild-type counterparts. Isolated cerebellar neurons natively expressed RGS6, GABA(B)R, and GIRK channel subunits, and cerebellar granule neurons from RGS6(-/-) mice showed a significant delay in the deactivation kinetics of baclofen-induced GIRK channel currents. These results establish RGS6 as a key component of GABA(B)R signaling and represent the first demonstration of an essential role for modulatory actions of RGS proteins in adult cerebellum. Dysregulation of RGS6 expression in human patients could potentially contribute to loss of motor coordination and, thus, pharmacological manipulation of RGS6 levels might represent a viable means to treat patients with ataxias of cerebellar origin.
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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.