Cloning and characterization of a novel NMDA receptor subunit NR3B: a dominant subunit that reduces calcium permeability

Matsuda, Keiko; Kamiya, Yoshinori; Matsuda, Shinji; Yuzaki, Michisuke

doi:10.1016/s0169-328x(02)00173-0

Cited by 170 publications

(157 citation statements)

References 39 publications

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“…N R3 (NRL or Ch i-1 ) is expressed predominantly in the developing CNS. NR3 does not seem to form functional homomeric Glu-activated channels, but the co-expression of NR3 with NR1 plus NR2 subunits decreases any response magnitude [334][335][336][337] .…”

Section: ) Synaptic Plasticitymentioning

confidence: 99%

A Review of Glutamate Receptors I: Current Understanding of Their Biology

Rousseaux

2008

J Toxicol Pathol

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Seventy years ago it was discovered that glutamate is abundant in the brain and that it plays a central role in brain metabolism. However, it took the scientific community a long time to realize that glutamate also acts as a neurotransmitter. Glutamate is an amino acid and brain tissue contains as much as 5 -15 mM glutamate per kg depending on the region, which is more than of any other amino acid. The main motivation for the ongoing research on glutamate is due to the role of glutamate in the signal transduction in the nervous systems of apparently all complex living organisms, including man. Glutamate is considered to be the major mediator of excitatory signals in the mammalian central nervous system and is involved in most aspects of normal brain function including cognition, memory and learning. In this review, the basic biology of the excitatory amino acids glutamate, glutamate receptors, GABA, and glycine will first be explored. In the second part of this review, the known pathophysiology and pathology will be described. (J Toxicol Pathol 2008; 21: 25-51)

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Section: ) Synaptic Plasticitymentioning

confidence: 99%

A Review of Glutamate Receptors I: Current Understanding of Their Biology

Rousseaux

2008

J Toxicol Pathol

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“…(NR1), GluR⑀1-GluR⑀4 (NR2A-NR2D) and GluR1-GluR2 (NR3A-NR3B) (Nakanishi, 1992;Sucher et al, 1995;Matsuda et al, 2002), 1, ⑀1, and ⑀2 subunits are most strongly expressed in the CA1 area of the adult rodent hippocampus (Monyer et al, 1994;Fritschy et al, 1998;Watanabe et al, 1998). Little is known, however, about quantitative distribution of synaptic ⑀ subunits in the hippocampus.…”

Section: Introductionmentioning

confidence: 99%

Target-Cell-Specific Left-Right Asymmetry of NMDA Receptor Content in Schaffer Collateral Synapses in ϵ1/NR2A Knock-Out Mice

Kawakami

Shinohara

et al. 2005

J. Neurosci.

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Input-dependent left-right asymmetry of NMDA receptor ⑀2 (NR2B) subunit allocation was discovered in hippocampal Schaffer collateral (Sch) and commissural fiber pyramidal cell synapses (Kawakami et al., 2003). To investigate whether this asymmetrical ⑀2 allocation is also related to the types of the postsynaptic cells, we compared postembedding immunogold labeling for ⑀2 in left and right Sch synapses on pyramidal cells and interneurons. To facilitate the detection of ⑀2 density difference, we used ⑀1 (NR2A) knock-out (KO) mice, which have a simplified NMDA receptor subunit composition.The labeling density for ⑀2 but not 1 (NR1) and subtype 2/3 glutamate receptor (GluR2/3) in Sch-CA1 pyramidal cell synapses was significantly different between the left and right hippocampus with opposite directions in strata oriens and radiatum; the left to right ratio of ⑀2 labeling density was 1:1.50 in stratum oriens and 1.44:1 in stratum radiatum. No significant difference, however, was detected in CA1 stratum radiatum between the left and right Sch-GluR4-positive (mostly parvalbumin-positive) and Sch-GluR4-negative interneuron synapses. Consistent with the anatomical asymmetry, the amplitude ratio of NMDA EPSCs to non-NMDA EPSCs in pyramidal cells was approximately two times larger in right than left stratum radiatum and vice versa in stratum oriens of ⑀1 KO mice. Moreover, the amplitude of long-term potentiation in the Sch-CA1 synapses of left stratum radiatum was significantly larger than that in the right corresponding synapses. These results indicate that the asymmetry of ⑀2 distribution is target cell specific, resulting in the left-right difference in NMDA receptor content and plasticity in Sch-CA1 pyramidal cell synapses in ⑀1 KO mice.

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“…Although NR1 serves as an essential component, members of the NR2 family bind ligand and differentially modulate receptor functions. The NR3 subunits exhibit an inhibitory role and form a glycine receptor when co-expressed with NR1 (4,5). In comparison to other family members, the NR2A subunit participates in the formation of an NMDA receptor complex that exhibits a rapid conduction (6 -8).…”

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confidence: 99%

Functional Analysis of the Rat N-Methyl-D-aspartate Receptor 2A Promoter

Liu

Zhuang

Hoffman

et al. 2003

Journal of Biological Chemistry

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N-Methyl-D-aspartate (NMDA) receptor subunit 2A (NR2A) is an important modulatory component of the NMDA subtype of glutamate receptors. To investigate the transcription mechanism of the NR2A gene, we cloned the 5 -flanking sequence from a rat genomic library. RNA mapping with rat brain RNA revealed two sets of major and several minor transcription start points in a single exon of 1140 bp. Reporter gene and mutation studies indicated that core promoter activity resided in exon 1, whereas the 5 -flanking sequence up to 1.5 kb showed no significant impact on promoter activity. Fragments containing minor transcription start points were able to drive a reporter gene in transfected cells and produce nascent RNAs in an in vitro transcription system. All fragments tested showed more promoter activity in dissociated neurons of the rat embryonic cerebrocortex and cell lines expressing NR2A mRNA than that in glial cultures and non-neuronal cells. Within exon 1 there are three GC-box elements that displayed distinct binding affinity to both Sp1-and Sp4-like factors. Overexpression of Sp1 or Sp4, but not Sp3, significantly increased the activity of the promoter containing these elements. Inclusion of exon 2 and 3 sequences, which contain five short open-reading frames, attenuated promoter-driven reporter activity more than 3-fold but attenuated the level of reporter mRNA less than 1.4-fold. Our results suggest that the core promoter of the rat NR2A gene requires exon 1, that Sp factors positively regulate this core promoter, and that a post-transcriptional mechanism may negatively regulate expression of the gene.

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Cloning and characterization of a novel NMDA receptor subunit NR3B: a dominant subunit that reduces calcium permeability

Cited by 170 publications

References 39 publications

A Review of Glutamate Receptors I: Current Understanding of Their Biology

A Review of Glutamate Receptors I: Current Understanding of Their Biology

Target-Cell-Specific Left-Right Asymmetry of NMDA Receptor Content in Schaffer Collateral Synapses in ϵ1/NR2A Knock-Out Mice

Functional Analysis of the Rat N-Methyl-D-aspartate Receptor 2A Promoter

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