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Principal role of NR3 subunits in NR1/NR3 excitatory glycine receptor function.
Biochem Biophys Res Commun. 2007 Mar 02; 354(1):102-8.BB

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.

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Authors+Show Affiliations

Madry C
Abteilung Neurochemie, Max-Planck-Institut für Hirnforschung, Deutschordenstr. 46, 60528 Frankfurt, Germany.
Mesic I
No affiliation info available
Bartholomäus I
No affiliation info available
Nicke A
No affiliation info available
Betz H
No affiliation info available
Laube B
No affiliation info available

MeSH

AnimalsGlycineOocytesProtein SubunitsReceptors, GlycineReceptors, N-Methyl-D-AspartateStructure-Activity RelationshipXenopus laevis

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17214961

Citation

Madry, Christian, et al. "Principal Role of NR3 Subunits in NR1/NR3 Excitatory Glycine Receptor Function." Biochemical and Biophysical Research Communications, vol. 354, no. 1, 2007, pp. 102-8.
Madry C, Mesic I, Bartholomäus I, et al. Principal role of NR3 subunits in NR1/NR3 excitatory glycine receptor function. Biochem Biophys Res Commun. 2007;354(1):102-8.
Madry, C., Mesic, I., Bartholomäus, I., Nicke, A., Betz, H., & Laube, B. (2007). Principal role of NR3 subunits in NR1/NR3 excitatory glycine receptor function. Biochemical and Biophysical Research Communications, 354(1), 102-8.
Madry C, et al. Principal Role of NR3 Subunits in NR1/NR3 Excitatory Glycine Receptor Function. Biochem Biophys Res Commun. 2007 Mar 2;354(1):102-8. PubMed PMID: 17214961.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Principal role of NR3 subunits in NR1/NR3 excitatory glycine receptor function. AU - Madry,Christian, AU - Mesic,Ivana, AU - Bartholomäus,Ingo, AU - Nicke,Annette, AU - Betz,Heinrich, AU - Laube,Bodo, Y1 - 2006/12/28/ PY - 2006/12/15/received PY - 2006/12/19/accepted PY - 2007/1/12/pubmed PY - 2007/4/7/medline PY - 2007/1/12/entrez SP - 102 EP - 8 JF - Biochemical and biophysical research communications JO - Biochem Biophys Res Commun VL - 354 IS - 1 N2 - 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. SN - 0006-291X UR - https://www.unboundmedicine.com/medline/citation/17214961/Principal_role_of_NR3_subunits_in_NR1/NR3_excitatory_glycine_receptor_function_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(06)02825-7 DB - PRIME DP - Unbound Medicine ER -