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Principal role of NR3 subunits in NR1/NR3 excitatory glycine receptor function.

Madry, Christian and Mesic, Ivana and Bartholomäus, Ingo and Nicke, Annette and Betz, Heinrich and Laube, Bodo (2007):
Principal role of NR3 subunits in NR1/NR3 excitatory glycine receptor function.
In: Biochemical and biophysical research communications, pp. 102-8, 354, (1), ISSN 0006-291X,
[Article]

Abstract

Calcium-permeable N-methyl-d-aspartate (NMDA) receptors are tetrameric cation channels composed of glycine-binding NR1 and glutamate-binding NR2 subunits, which require binding of both glutamate and glycine for efficient channel gating. In contrast, receptors assembled from NR1 and NR3 subunits function as calcium-impermeable excitatory glycine receptors that respond to agonist application only with low efficacy. Here, we show that antagonists of and substitutions within the glycine-binding site of NR1 potentiate NR1/NR3 receptor function up to 25-fold, but inhibition or mutation of the NR3 glycine binding site reduces or abolishes receptor activation. Thus, glycine bound to the NR1 subunit causes auto-inhibition of NR1/NR3 receptors whereas glycine binding to the NR3 subunits is required for opening of the ion channel. Our results establish differential roles of the high-affinity NR3 and low-affinity NR1 glycine-binding sites in excitatory glycine receptor function.

Item Type: Article
Erschienen: 2007
Creators: Madry, Christian and Mesic, Ivana and Bartholomäus, Ingo and Nicke, Annette and Betz, Heinrich and Laube, Bodo
Title: Principal role of NR3 subunits in NR1/NR3 excitatory glycine receptor function.
Language: English
Abstract:

Calcium-permeable N-methyl-d-aspartate (NMDA) receptors are tetrameric cation channels composed of glycine-binding NR1 and glutamate-binding NR2 subunits, which require binding of both glutamate and glycine for efficient channel gating. In contrast, receptors assembled from NR1 and NR3 subunits function as calcium-impermeable excitatory glycine receptors that respond to agonist application only with low efficacy. Here, we show that antagonists of and substitutions within the glycine-binding site of NR1 potentiate NR1/NR3 receptor function up to 25-fold, but inhibition or mutation of the NR3 glycine binding site reduces or abolishes receptor activation. Thus, glycine bound to the NR1 subunit causes auto-inhibition of NR1/NR3 receptors whereas glycine binding to the NR3 subunits is required for opening of the ion channel. Our results establish differential roles of the high-affinity NR3 and low-affinity NR1 glycine-binding sites in excitatory glycine receptor function.

Journal or Publication Title: Biochemical and biophysical research communications
Volume: 354
Number: 1
Divisions: 10 Department of Biology
10 Department of Biology > Neurophysiology and Neurosensory Systems
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Date Deposited: 11 Apr 2011 09:26
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