Molecular characterization of the family of the N-methyl-D-aspartate receptor subunits

T. Ishii, K. Moriyoshi, H. Sugihara, K. Sakurada, H. Kadotani, M. Yokoi, C. Akazawa, R. Shigemoto, N. Mizuno, M. Masu, S. Nakanishi

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903 Citations (Scopus)

Abstract

cDNA clones for four different N-methyl-D-aspartate (NMDA) receptor subunits (NMDAR2A-NMDAR2D) were isolated through polymerase chain reactions followed by molecular screening of a rat brain cDNA library. These subunits are only about 15% identical with the key subunit of the NMDA receptor (NMDAR1) but are highly homologous (~50% homology) with one another. They also commonly possess large hydrophilic domains at both amino- and carboxyl- terminal sides of the four putative transmembrane segments. NMDAR2A and NMDAR2C expressed individually in Xenopus oocytes showed no electrophysiological response to agonists. However, these subunits in combined expression with NMDAR1 markedly potentiated the NMDAR1 activity and produced functional variability in the affinity of agonists, the effectiveness of antagonists, and the sensitivity to Mg2+ blockade. Thus, NMDAR1 is essential for the function of the NMDA receptor, and multiple NMDAR2 subunits potentiate and differentiate the function of the NMDA receptor by forming different heteromeric configurations with NMDAR1. Northern blotting and in situ hybridization analyses revealed that the expressions of individual mRNAs for the NMDAR2 subunits overlap in some brain regions but are also specialized in many other regions. This investigation demonstrates the anatomical and functional differences of the NMDAR2 subunits, which provide the molecular basis for the functional diversity of the NMDA receptor.

Original languageEnglish
Pages (from-to)2836-2843
Number of pages8
JournalJournal of Biological Chemistry
Volume268
Issue number4
Publication statusPublished - 1993
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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