Phosphorylation-dependent regulation of N-methyl-D-aspartate receptors by calmodulin

Chihiro Hisatsune, Hisashi Umemori, Takafumi Inoue, Takayuki Michikawa, Kazuhisa Kohda, Katsuhiko Mikoshiba, Tadashi Yamamoto

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106 Citations (Scopus)

Abstract

The N-methyl-D-aspartate (NMDA) receptor plays important roles in synaptic plasticity and brain development. The NMDA receptor subunits have large intracellular domains in the COOH-terminal region that may interact with signal-transducing proteins. By using the yeast two-hybrid system, we found that calmodulin interacts with the COOH terminus of the NR1 subunit and inactivates the channels in a Ca2+-dependent manner. Here we show that protein kinase C (PKC)-mediated phosphorylation on serine residues of NR1 decreases its affinity for calmodulin. This suggests that PKC-mediated phosphorylation of NR1 prevents calmodulin from binding to the NR1 subunit and thereby inhibits the inactivation of NMDA receptors by calmodulin. In addition, we show that stimulation of metabotropic glutamate receptor 1α, which potentiates NMDA channels through PKC, decreases the ability of NR1 to bind to calmodulin. Thus, our data provide clues to understanding the basis of cross-talk between two types of receptors, metabotropic glutamate receptors and the NR1 subunit, in NMDA channel potentiation.

Original languageEnglish
Pages (from-to)20805-20810
Number of pages6
JournalJournal of Biological Chemistry
Volume272
Issue number33
DOIs
Publication statusPublished - 1997 Aug 15

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Hisatsune, C., Umemori, H., Inoue, T., Michikawa, T., Kohda, K., Mikoshiba, K., & Yamamoto, T. (1997). Phosphorylation-dependent regulation of N-methyl-D-aspartate receptors by calmodulin. Journal of Biological Chemistry, 272(33), 20805-20810. https://doi.org/10.1074/jbc.272.33.20805