Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Proc Natl Acad Sci U S A
2008 Aug 26;10534:12563-8. doi: 10.1073/pnas.0805624105.
Show Gene links
Show Anatomy links
Supralinear potentiation of NR1/NR3A excitatory glycine receptors by Zn2+ and NR1 antagonist.
Madry C
,
Betz H
,
Geiger JR
,
Laube B
.
???displayArticle.abstract???
Coassembly of the glycine-binding NMDA receptor subunits NR1 and NR3A results in excitatory glycine receptors of low efficacy. Here, we report that micromolar concentrations of the divalent cation Zn(2+) produce a 10-fold potentiation of NR1/NR3A receptor responses, which resembles that seen upon antagonizing glycine binding to the NR1 subunit. Coapplication of both Zn(2+) and NR1 antagonist caused a supralinear potentiation, resulting in a >120-fold increase of glycine-activated currents. At concentrations >50 microM, Zn(2+) alone generated receptor currents with similar efficacy as glycine, implying that NR1/NR3A receptors can be activated by different agonists. Point mutations in the NR1 and NR3A glycine-binding sites revealed that both the potentiating and agonistic effects of Zn(2+) are mediated by the ligand-binding domain of the NR1 subunit. In conclusion, Zn(2+) acts as a potent positive modulator and agonist at the NR1 subunit of NR1/NR3A receptors. Our results suggest that this unconventional member of the NMDA receptor family may in vivo be gated by the combined action of glycine and Zn(2+) or a yet unknown second ligand.
Awobuluyi,
Subunit-specific roles of glycine-binding domains in activation of NR1/NR3 N-methyl-D-aspartate receptors.
2007, Pubmed
Awobuluyi,
Subunit-specific roles of glycine-binding domains in activation of NR1/NR3 N-methyl-D-aspartate receptors.
2007,
Pubmed
Changeux,
Allosteric receptors after 30 years.
1998,
Pubmed
Chatterton,
Excitatory glycine receptors containing the NR3 family of NMDA receptor subunits.
2002,
Pubmed
,
Xenbase
Collingridge,
Memories of NMDA receptors and LTP.
1995,
Pubmed
Cull-Candy,
Role of distinct NMDA receptor subtypes at central synapses.
2004,
Pubmed
Das,
Increased NMDA current and spine density in mice lacking the NMDA receptor subunit NR3A.
1998,
Pubmed
,
Xenbase
Frederickson,
Synaptic release of zinc from brain slices: factors governing release, imaging, and accurate calculation of concentration.
2006,
Pubmed
Furukawa,
Subunit arrangement and function in NMDA receptors.
2005,
Pubmed
Henson,
Developmental regulation of the NMDA receptor subunits, NR3A and NR1, in human prefrontal cortex.
2008,
Pubmed
Hirzel,
Hyperekplexia phenotype of glycine receptor alpha1 subunit mutant mice identifies Zn(2+) as an essential endogenous modulator of glycinergic neurotransmission.
2006,
Pubmed
Johnson,
Glycine potentiates the NMDA response in cultured mouse brain neurons.
,
Pubmed
Káradóttir,
NMDA receptors are expressed in oligodendrocytes and activated in ischaemia.
2005,
Pubmed
Kuryatov,
Mutational analysis of the glycine-binding site of the NMDA receptor: structural similarity with bacterial amino acid-binding proteins.
1994,
Pubmed
,
Xenbase
Laube,
Evidence for a tetrameric structure of recombinant NMDA receptors.
1998,
Pubmed
,
Xenbase
Laube,
Modulation by zinc ions of native rat and recombinant human inhibitory glycine receptors.
1995,
Pubmed
,
Xenbase
Le Novère,
Models of the extracellular domain of the nicotinic receptors and of agonist- and Ca2+-binding sites.
2002,
Pubmed
Madden,
The structure and function of glutamate receptor ion channels.
2002,
Pubmed
Madry,
Principal role of NR3 subunits in NR1/NR3 excitatory glycine receptor function.
2007,
Pubmed
,
Xenbase
Madry,
The N-terminal domains of both NR1 and NR2 subunits determine allosteric Zn2+ inhibition and glycine affinity of N-methyl-D-aspartate receptors.
2007,
Pubmed
,
Xenbase
Matsuda,
Specific assembly with the NMDA receptor 3B subunit controls surface expression and calcium permeability of NMDA receptors.
2003,
Pubmed
Mayer,
Glutamate receptors at atomic resolution.
2006,
Pubmed
Micu,
NMDA receptors mediate calcium accumulation in myelin during chemical ischaemia.
2006,
Pubmed
Miller,
Molecular basis for zinc potentiation at strychnine-sensitive glycine receptors.
2005,
Pubmed
Mueller,
NR3A NMDA receptor subunit mRNA expression in schizophrenia, depression and bipolar disorder.
2004,
Pubmed
Nakanishi,
Molecular diversity of glutamate receptors and implications for brain function.
1992,
Pubmed
Paoletti,
High-affinity zinc inhibition of NMDA NR1-NR2A receptors.
1997,
Pubmed
,
Xenbase
Paoletti,
Molecular organization of a zinc binding n-terminal modulatory domain in a NMDA receptor subunit.
2000,
Pubmed
,
Xenbase
Perez-Otano,
Assembly with the NR1 subunit is required for surface expression of NR3A-containing NMDA receptors.
2001,
Pubmed
Rachline,
The micromolar zinc-binding domain on the NMDA receptor subunit NR2B.
2005,
Pubmed
,
Xenbase
Salter,
NMDA receptors are expressed in developing oligodendrocyte processes and mediate injury.
2005,
Pubmed
Schüler,
Formation of NR1/NR2 and NR1/NR3 heterodimers constitutes the initial step in N-methyl-D-aspartate receptor assembly.
2008,
Pubmed
,
Xenbase
Stoll,
Differential regulation of ionotropic glutamate receptors.
2007,
Pubmed
Stys,
White matter NMDA receptors: an unexpected new therapeutic target?
2007,
Pubmed
Tong,
Modulation of NMDA receptor properties and synaptic transmission by the NR3A subunit in mouse hippocampal and cerebrocortical neurons.
2008,
Pubmed
,
Xenbase
Yao,
Characterization of a soluble ligand binding domain of the NMDA receptor regulatory subunit NR3A.
2006,
Pubmed
Zheng,
Allosteric interaction between the amino terminal domain and the ligand binding domain of NR2A.
2001,
Pubmed
