Evidence map›Paper›PMID 32179786›Full record

ArticleScientific reports2020

Modulation of glycine receptor single-channel conductance by intracellular phosphorylation.

Gustavo Moraga-Cid, Victoria P San Martín, Cesar O Lara, Braulio Muñoz, Ana M Marileo, Anggelo Sazo, Carola Muñoz-Montesino, Jorge Fuentealba, Patricio A Castro, Leonardo Guzmán and 5 more

Open access · goldAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.5field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 38 citations in OpenAlex.

  1. Human GlyRα2 pore dynamics in gating and inhibition.Structure (London, England : 1993) · 2026
    Article
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  4. Review
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  6. Article
  7. Gating mechanism of the human α1β GlyR by glycine.Structure (London, England : 1993) · 2024
    Article
  8. Article
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  10. Review
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  15. Article
  16. Allosteric modulation of alternatively spliced CaProceedings of the National Academy of Sciences of the United States of America · 2020
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 4 institutions in 4 countries.

Gustavo Moraga-Cid *Department of Physiology, Faculty of Biological Sciences, University of Concepción, Concepción, Chile. gumoraga@udec.cl.
Victoria P San Martín *Department of Physiology, Faculty of Biological Sciences, University of Concepción, Concepción, Chile.
Cesar O LaraDepartment of Physiology, Faculty of Biological Sciences, University of Concepción, Concepción, Chile.
Braulio MuñozDepartment of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Ana M MarileoDepartment of Physiology, Faculty of Biological Sciences, University of Concepción, Concepción, Chile.
Anggelo SazoDepartment of Physiology, Faculty of Biological Sciences, University of Concepción, Concepción, Chile.
Carola Muñoz-MontesinoDepartment of Physiology, Faculty of Biological Sciences, University of Concepción, Concepción, Chile.
Jorge FuentealbaDepartment of Physiology, Faculty of Biological Sciences, University of Concepción, Concepción, Chile.
Patricio A CastroDepartment of Physiology, Faculty of Biological Sciences, University of Concepción, Concepción, Chile.
Leonardo GuzmánDepartment of Physiology, Faculty of Biological Sciences, University of Concepción, Concepción, Chile.
Carlos F BurgosDepartment of Physiology, Faculty of Biological Sciences, University of Concepción, Concepción, Chile.
Hanns U ZeilhoferInstitute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, CH-8057, Zürich, Switzerland.
Luis G AguayoDepartment of Physiology, Faculty of Biological Sciences, University of Concepción, Concepción, Chile.
Pierre-Jean CorringerChannel-Receptors Unit, Institute Pasteur, UMR 3571 CNRS, 75015, Paris, France.
Gonzalo E YévenesDepartment of Physiology, Faculty of Biological Sciences, University of Concepción, Concepción, Chile. gyevenes@udec.cl.
University of Concepción · CLETH Zurich · CHIndiana University – Purdue University Indianapolis · USInstitut Pasteur · FR

Funding

Mechanisms for potentiation of glycine receptors by ethanol.R01AA025718 · NIAAA · UNIVERSITY OF CONCEPCION · PI AGUAYO, LUIS GERARDO · 2017 to 2021
$1.1M
NIAAA NIH HHS R01 AA025718
6 · The paper itself

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.

Indexed as

Excitatory Postsynaptic PotentialsAmino Acid SubstitutionCyclic AMP-Dependent Protein KinasesHumansIntracellular SpacePhosphorylationProtein DomainsProtein Processing, Post-TranslationalReceptors, GlycineReceptors, Prostaglandin E, EP2 SubtypeSignal TransductionCyclic AMP-Dependent Protein Kinasesglycine receptor alpha3 subunitPTGER2 protein, humanReceptors, GlycineReceptors, Prostaglandin E, EP2 Subtype

Identifiers

PMID32179786
PMCPMC7076024
OpenAlexW3012128682

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.