ArticleThe Journal of biological chemistry2010
Molecular requirements for ethanol differential allosteric modulation of glycine receptors based on selective Gbetagamma modulation.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 52 citations in OpenAlex.
- Milestone Review: Unlocking the Proteomics of Glycine Receptor Complexes.Journal of neurochemistry · 2025Review
- Allosteric modulation and direct activation of glycine receptors by a tricyclic sulfonamide.Scientific reports · 2025Article
- Changes in ethanol effects in knock-in mice expressing ethanol insensitive alpha1 and alpha2 glycine receptor subunits.Life sciences · 2024Article
- Loss of glycine receptors in the nucleus accumbens and ethanol reward in an Alzheimer´s Disease mouse model.Progress in neurobiology · 2024Article
- Positive Allosteric Modulators of Glycine Receptors and Their Potential Use in Pain Therapies.Pharmacological reviews · 2022Review
- Presence of ethanol-sensitive and ethanol-insensitive glycine receptors in the ventral tegmental area and prefrontal cortex in mice.British journal of pharmacology · 2021Article
- Reduced sedation and increased ethanol consumption in knock-in mice expressing an ethanol insensitive alpha 2 subunit of the glycine receptor.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Article
- Modulatory Actions of the Glycine Receptor β Subunit on the Positive Allosteric Modulation of Ethanol in α2 Containing Receptors.Frontiers in molecular neuroscience · 2021Article
- Contribution of GlyR α3 Subunits to the Sensitivity and Effect of Ethanol in the Nucleus Accumbens.Frontiers in molecular neuroscience · 2021Article
- Ethanol consumption and sedation are altered in mice lacking the glycine receptor α2 subunit.British journal of pharmacology · 2020Article
- Influence of nonsynaptic α1 glycine receptors on ethanol consumption and place preference.Addiction biology · 2020Article
- High ethanol sensitive glycine receptors regulate firing in D1 medium spiny neurons in the nucleus accumbens.Neuropharmacology · 2019Article
- Permeating disciplines: Overcoming barriers between molecular simulations and classical structure-function approaches in biological ion transport.Biochimica et biophysica acta. Biomembranes · 2018Review
- Presence of ethanol-sensitive glycine receptors in medium spiny neurons in the mouse nucleus accumbens.The Journal of physiology · 2017Article
- Dual activation of neuronal G protein-gated inwardly rectifying potassium (GIRK) channels by cholesterol and alcohol.Scientific reports · 2017Article
- Structural Basis of Alcohol Inhibition of the Pentameric Ligand-Gated Ion Channel ELIC.Structure (London, England : 1993) · 2017Article
- Structure-Function Analysis of the GlyR α2 Subunit Autism Mutation p.R323L Reveals a Gain-of-Function.Frontiers in molecular neuroscience · 2017Article
- Structure and Pharmacologic Modulation of Inhibitory Glycine Receptors.Molecular pharmacology · 2016Review
- Functional modulation of glycine receptors by the alkaloid gelsemine.British journal of pharmacology · 2016Article
- The TRPM1 channel in ON-bipolar cells is gated by both the α and the βγ subunits of the G-protein Go.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
It is now believed that the allosteric modulation produced by ethanol in glycine receptors (GlyRs) depends on alcohol binding to discrete sites within the protein structure. Thus, the differential ethanol sensitivity of diverse GlyR isoforms and mutants was explained by the presence of specific residues in putative alcohol pockets. Here, we demonstrate that ethanol sensitivity in two ligand-gated ion receptor members, the GlyR adult α(1) and embryonic α(2) subunits, can be modified through selective mutations that rescued or impaired Gβγ modulation. Even though both isoforms were able to physically interact with Gβγ, only the α(1) GlyR was functionally modulated by Gβγ and pharmacological ethanol concentrations. Remarkably, the simultaneous switching of two transmembrane and a single extracellular residue in α(2) GlyRs was enough to generate GlyRs modulated by Gβγ and low ethanol concentrations. Interestingly, although we found that these TM residues were different to those in the alcohol binding site, the extracellular residue was recently implicated in conformational changes important to generate a pre-open-activated state that precedes ion channel gating. Thus, these results support the idea that the differential ethanol sensitivity of these two GlyR isoforms rests on conformational changes in transmembrane and extracellular residues within the ion channel structure rather than in differences in alcohol binding pockets. Our results describe the molecular basis for the differential ethanol sensitivity of two ligand-gated ion receptor members based on selective Gβγ modulation and provide a new mechanistic framework for allosteric modulations of abuse drugs.
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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.