ArticleScientific reports2020
Modulation of glycine receptor single-channel conductance by intracellular phosphorylation.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 38 citations in OpenAlex.
- Human GlyRα2 pore dynamics in gating and inhibition.Structure (London, England : 1993) · 2026Article
- Article
- Mechanism of human α3β GlyR regulation by intracellular M3/M4 loop phosphorylation and 2,6-di-tert-butylphenol interaction.Nature communications · 2025Article
- Beyond the hype: a comprehensive exploration of CBD's biological impacts and mechanisms of action.Journal of cannabis research · 2025Review
- Allosteric modulation and direct activation of glycine receptors by a tricyclic sulfonamide.Scientific reports · 2025Article
- Molecular investigation of ergot alkaloid ergotamine's modulatory effects on glycine receptors expressed inComputational and structural biotechnology journal · 2025Article
- Gating mechanism of the human α1β GlyR by glycine.Structure (London, England : 1993) · 2024Article
- Modelling and Molecular Dynamics Predict the Structure and Interactions of the Glycine Receptor Intracellular Domain.Biomolecules · 2023Article
- AAV-glycine receptor α3 alleviates CFA-induced inflammatory pain by downregulating ERK phosphorylation and proinflammatory cytokine expression in SD rats.Molecular medicine (Cambridge, Mass.) · 2023Article
- Positive Allosteric Modulators of Glycine Receptors and Their Potential Use in Pain Therapies.Pharmacological reviews · 2022Review
- Glycine Receptor Subtypes and Their Roles in Nociception and Chronic Pain.Frontiers in molecular neuroscience · 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
- Glycine Receptors in Spinal Nociceptive Control-An Update.Biomolecules · 2021Review
- A proline-rich motif in the large intracellular loop of the glycine receptor α1 subunit interacts with the Pleckstrin homology domain of collybistin.Journal of advanced research · 2021Article
- Effects of Interleukin-1β in Glycinergic Transmission at the Central Amygdala.Frontiers in pharmacology · 2021Article
- Allosteric modulation of alternatively spliced CaProceedings of the National Academy of Sciences of the United States of America · 2020Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 4 countries.
Funding
Abstract
Glycine receptors (GlyRs) are anion-permeable pentameric ligand-gated ion channels (pLGICs). The GlyR activation is critical for the control of key neurophysiological functions, such as motor coordination, respiratory control, muscle tone and pain processing. The relevance of the GlyR function is further highlighted by the presence of abnormal glycinergic inhibition in many pathophysiological states, such as hyperekplexia, epilepsy, autism and chronic pain. In this context, previous studies have shown that the functional inhibition of GlyRs containing the α3 subunit is a pivotal mechanism of pain hypersensitivity. This pathway involves the activation of EP2 receptors and the subsequent PKA-dependent phosphorylation of α3GlyRs within the intracellular domain (ICD), which decrease the GlyR-associated currents and enhance neuronal excitability. Despite the importance of this mechanism of glycinergic dis-inhibition associated with dysfunctional α3GlyRs, our current understanding of the molecular events involved is limited. Here, we report that the activation of PKA signaling pathway decreases the unitary conductance of α3GlyRs. We show in addition that the substitution of the PKA-targeted serine with a negatively charged residue within the ICD of α3GlyRs and of chimeric receptors combining bacterial GLIC and α3GlyR was sufficient to generate receptors with reduced conductance. Thus, our findings reveal a potential biophysical mechanism of glycinergic dis-inhibition and suggest that post-translational modifications of the ICD, such as phosphorylation, may shape the conductance of other pLGICs.
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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.