کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8516264 | 1556574 | 2018 | 45 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Chloride ions stabilize the glutamate-induced active state of the metabotropic glutamate receptor 3
ترجمه فارسی عنوان
یون های کلرید حالت فعال ناشی از گلوتامات گیرنده 3 گلوتامات متابوتروپیک را تثبیت می کنند
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب رفتاری
چکیده انگلیسی
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 Clâ 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, Clâ 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 Clâmediated amplified response to low ambient glutamate concentrations, such as those measured in cell media. This strong interaction between glutamate and Clâ 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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 140, 15 September 2018, Pages 275-286
Journal: Neuropharmacology - Volume 140, 15 September 2018, Pages 275-286
نویسندگان
Amélie S. Tora, Xavier Rovira, Anne-Marinette Cao, Alexandre Cabayé, Linnéa Olofsson, Fanny Malhaire, Pauline Scholler, Hayeon Baik, Ann Van Eeckhaut, Ilse Smolders, Philippe Rondard, Emmanuel Margeat, Francine Acher, Jean-Philippe Pin, Cyril Goudet,