Chloride ions stabilize the glutamate-induced active state of the metabotropic glutamate receptor 3
| العنوان: | Chloride ions stabilize the glutamate-induced active state of the metabotropic glutamate receptor 3 |
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| المؤلفون: | Jean-Philippe Pin, Ann Van Eeckhaut, Pauline Scholler, Ilse Julia Smolders, Emmanuel Margeat, Linnea Olofsson, Alexandre Cabayé, Philippe Rondard, Fanny Malhaire, Amélie S. Tora, Xavier Rovira, Cyril Goudet, Anne-Marinette Cao, Francine Acher, Hayeon Baik |
| المساهمون: | Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Universitat de Vic, Centre de Biochimie Structurale [Montpellier] (CBS), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Vrije Universiteit [Brussels] (VUB), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Vrije Universiteit Brussel (VUB), Pharmaceutical and Pharmacological Sciences, Experimental Pharmacology, Alliance for Modulation in Epilepsy |
| المصدر: | Neuropharmacology Neuropharmacology, Elsevier, 2018, 140, pp.275-286. ⟨10.1016/j.neuropharm.2018.08.011⟩ |
| بيانات النشر: | Elsevier BV, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Agonist, medicine.drug_class, Allosteric regulation, Glutamic Acid, Chloride, Radioligand Assay, 03 medical and health sciences, Cellular and Molecular Neuroscience, GPCR, Allosteric Regulation, Chlorides, Constitutive activity, Inosine Monophosphate, medicine, Humans, Receptors, AMPA, Allostery, Receptor, Cells, Cultured, G protein-coupled receptor, Pharmacology, Binding Sites, Chemistry, Glutamate receptor, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, 030104 developmental biology, Metabotropic glutamate receptor, Luminescent Measurements, Mutation, Excitatory postsynaptic potential, Biophysics, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Metabotropic glutamate receptor 3, Glutamate |
| الوصف: | International audience; Due to the essential roles of glutamate, detection and response to a large range of extracellular concentrations of this excitatory amino acid are necessary for the fine-tuning of brain functions. Metabotropic glutamate receptors (mGluRs) are implicated in shaping the activity of many synapses in the central nervous system. Among the eight mGluR subtypes, there is increasing interest in studying the mGlu3 receptor which has recently been linked to various diseases, including psychiatric disorders. This receptor displays striking functional properties, with a high and, often, full basal activity, making its study elusive in heterologous systems. Here, we demonstrate that Cl− ions exert strong positive allosteric modulation of glutamate on the mGlu3 receptor. We have also identified the molecular and structural determinants lying behind this allostery: a unique interactive “chloride-lock” network. Indeed, Cl− ions dramatically stabilize the glutamate-induced active state of the extracellular domain of the mGlu3 receptor. Thus, the mGlu3 receptors’ large basal activity does not correspond to a constitutive activity in absence of agonist. Instead, it results mostly from a Cl−mediated amplified response to low ambient glutamate concentrations, such as those measured in cell media. This strong interaction between glutamate and Cl− ions allows the mGlu3 receptor to sense and efficiently react to sub-micromolar concentrations of glutamate, making it the most sensitive member of mGluR family. |
| تدمد: | 0028-3908 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::19129dadf8c46c06f0a4f36a157b3f6a https://doi.org/10.1016/j.neuropharm.2018.08.011 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....19129dadf8c46c06f0a4f36a157b3f6a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00283908 |
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