ArticleThe Journal of biological chemistry2019
The signaling proteins GPR158 and RGS7 modulate excitability of L2/3 pyramidal neurons and control A-type potassium channel in the prelimbic cortex.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- Cognitive Deficits in Female GPR158 Knockout Mice Revealed by Automated Home-Cage Testing.Genes, brain, and behavior · 2026Article
- Synaptic Plasticity-Intrinsic Excitability and Antidepressant Discovery.Biomedicines · 2026Review
- Multiplexed changes in synaptic transmission underlie stress-induced reduction of persistent firing in the parietal cortex.Progress in neurobiology · 2026Article
- Crosstalk between bone and brain in Alzheimer's disease: Mechanisms, applications, and perspectives.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Review
- Glycine-induced activation of GPR158 increases the intrinsic excitability of medium spiny neurons in the nucleus accumbens.Cellular and molecular life sciences : CMLS · 2024Article
- Neurotrophin-3 from the dentate gyrus supports postsynaptic sites of mossy fiber-CA3 synapses and hippocampus-dependent cognitive functions.Molecular psychiatry · 2024Article
- Orphan peptide and G protein-coupled receptor signalling in alcohol use disorder.British journal of pharmacology · 2024Review
- Orphan receptor GPR158 serves as a metabotropic glycine receptor: mGlyR.Science (New York, N.Y.) · 2023Article
- Expression Mapping and Functional Analysis of Orphan G-Protein-Coupled Receptor GPR158 in the Adult Mouse Brain Using a GPR158 Transgenic Mouse.Biomolecules · 2023Article
- Adaptation of prelimbic cortex mediated by IL-6/STAT3/Acp5 pathway contributes to the comorbidity of neuropathic pain and depression in rats.Journal of neuroinflammation · 2022Article
- Review
- Cryo-EM structure of human GPR158 receptor coupled to the RGS7-Gβ5 signaling complex.Science (New York, N.Y.) · 2022Article
- Update on GPCR-based targets for the development of novel antidepressants.Molecular psychiatry · 2022Review
- Posterior cingulate cortex reveals an expression profile of resilience in cognitively intact elders.Brain communications · 2022Article
- Orphans to the rescue: orphan G-protein coupled receptors as new antidepressant targets.Journal of psychiatry & neuroscience : JPN · 2020Article
- Review
- Regulators of G-protein signaling, RGS2 and RGS4, inhibit protease-activated receptor 4-mediated signaling by forming a complex with the receptor and Gα in live cells.Cell communication and signaling : CCS · 2020Article
- rs12411980 single-nucleotide polymorphism related toMolecular painArticle
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Stress profoundly affects physiological properties of neurons across brain circuits and thereby increases the risk for depression. However, the molecular and cellular mechanisms mediating these effects are poorly understood. In this study, we report that chronic physical restraint stress in mice decreases excitability specifically in layer 2/3 of pyramidal neurons within the prelimbic subarea of the prefrontal cortex (PFC) accompanied by the induction of depressive-like behavioral states. We found that a complex between G protein-coupled receptor (GPCR) 158 (GPR158) and regulator of G protein signaling 7 (RGS7), a regulatory GPCR signaling node recently discovered to be a key modulator of affective behaviors, plays a key role in controlling stress-induced changes in excitability in this neuronal population. Deletion of GPR158 or RGS7 enhanced excitability of layer 2/3 PFC neurons and prevented the impact of stress. Investigation of the underlying molecular mechanisms revealed that the A-type potassium channel Kv4.2 subunit is a molecular target of the GPR158-RGS7 complex. We further report that GPR158 physically associates with Kv4.2 channel and promotes its function by suppressing inhibitory modulation by cAMP-protein kinase A (PKA)-mediated phosphorylation. Taken together, our observations reveal a critical mechanism that adjusts neuronal excitability in L2/3 pyramidal neurons of the PFC and may thereby modulate the effects of stress on depression.
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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.