ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2014
Regulator of G-protein signaling 6 (RGS6) promotes anxiety and depression by attenuating serotonin-mediated activation of the 5-HT(1A) receptor-adenylyl cyclase axis.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 49 citations in OpenAlex.
- Regulator of G protein signaling 6 (RGS6) controls the effect of cannabinoids on intestinal tract motility and visceral pain sensation in mice.Pharmacological reports : PR · 2026Article
- Placental DNA methylation captures shared and trait-specific genetic susceptibility across complex health conditions.medRxiv : the preprint server for health sciences · 2026Article
- Genome-wide by trait interaction analyses with neuroticism reveal chronic pain-associated depression as a distinct genetic subtype.Translational psychiatry · 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
- Melatonin ameliorates inflammation-induced developmental defects of enamel by upregulating regulator of G protein signaling 2.Journal of dental sciences · 2024Article
- Low-level brain somatic mutations in exonic regions are collectively implicated in autism with germline mutations in autism risk genes.Experimental & molecular medicine · 2024Article
- A splice acceptor variant in RGS6 associated with intellectual disability, microcephaly, and cataracts disproportionately promotes expression of a subset of RGS6 isoforms.Journal of human genetics · 2024Article
- 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
- Genes positively regulated by Mef2c in cortical neurons are enriched for common genetic variation associated with IQ and educational attainment.Human molecular genetics · 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
- 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
- Article
- The Combination ofFrontiers in pharmacology · 2020Article
- Regulator of G-protein signaling (RGS) proteins as drug targets: Progress and future potentials.The Journal of biological chemistry · 2019Review
- Age-dependent nigral dopaminergic neurodegeneration and α-synuclein accumulation in RGS6-deficient mice.JCI insight · 2019Article
- Homeostatic cAMP regulation by the RGS7 complex controls depression-related behaviors.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2019Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Targeting serotonin (5-HT) bioavailability with selective 5-HT reuptake inhibitors (SSRIs) remains the most widely used treatment for mood disorders. However, their limited efficacy, delayed onset of action, and side effects restrict their clinical utility. Endogenous regulator of G-protein signaling (RGS) proteins have been implicated as key inhibitors of 5-HT(1A)Rs, whose activation is believed to underlie the beneficial effects of SSRIs, but the identity of the specific RGS proteins involved remains unknown. We identify RGS6 as the critical negative regulator of 5-HT(1A)R-dependent antidepressant actions. RGS6 is enriched in hippocampal and cortical neurons, 5-HT(1A)R-expressing cells implicated in mood disorders. RGS6(-/-) mice exhibit spontaneous anxiolytic and antidepressant behavior rapidly and completely reversibly by 5-HT(1A)R blockade. Effects of the SSRI fluvoxamine and 5-HT(1A)R agonist 8-OH-DPAT were also potentiated in RGS6(+/-) mice. The phenotype of RGS6(-/-) mice was associated with decreased CREB phosphorylation in the hippocampus and cortex, implicating enhanced Gα(i)-dependent adenylyl cyclase inhibition as a possible causative factor in the behavior observed in RGS6(-/-) animals. Our results demonstrate that by inhibiting serotonergic innervation of the cortical-limbic neuronal circuit, RGS6 exerts powerful anxiogenic and prodepressant actions. These findings indicate that RGS6 inhibition may represent a viable means to treat mood disorders or enhance the efficacy of serotonergic agents.
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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.