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

Research output: Contribution to journalArticle

105 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
Externally publishedYes

Fingerprint

Phosphorylation
Calmodulin
N-Methyl-D-Aspartate Receptors
Protein Kinase C
N-Methylaspartate
Two-Hybrid System Techniques
Metabotropic Glutamate Receptors
Neuronal Plasticity
Hybrid systems
Yeast
Serine
Plasticity
Brain
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

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

Phosphorylation-dependent regulation of N-methyl-D-aspartate receptors by calmodulin. / Hisatsune, Chihiro; Umemori, Hisashi; Inoue, Takafumi; Michikawa, Takayuki; Kohda, Kazuhisa; Mikoshiba, Katsuhiko; Yamamoto, Tadashi.

In: Journal of Biological Chemistry, Vol. 272, No. 33, 15.08.1997, p. 20805-20810.

Research output: Contribution to journalArticle

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, vol. 272, no. 33, pp. 20805-20810. https://doi.org/10.1074/jbc.272.33.20805
Hisatsune, Chihiro ; Umemori, Hisashi ; Inoue, Takafumi ; Michikawa, Takayuki ; Kohda, Kazuhisa ; Mikoshiba, Katsuhiko ; Yamamoto, Tadashi. / Phosphorylation-dependent regulation of N-methyl-D-aspartate receptors by calmodulin. In: Journal of Biological Chemistry. 1997 ; Vol. 272, No. 33. pp. 20805-20810.
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