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Review
. 2007 Sep;53(3):362-8.
doi: 10.1016/j.neuropharm.2007.05.018. Epub 2007 Jun 2.

Regulation of NMDA receptors by phosphorylation

Bo-Shiun Chen  1 , Katherine W Roche
Affiliations
Review

Regulation of NMDA receptors by phosphorylation

Bo-Shiun Chen et al. Neuropharmacology. 2007 Sep.

Abstract

N-methyl-D-aspartate (NMDA) receptors are critical for neuronal development and synaptic plasticity. The molecular mechanisms underlying the synaptic localization and functional regulation of NMDA receptors have been the subject of extensive studies. In particular, phosphorylation has emerged as a fundamental mechanism that regulates NMDA receptor trafficking and can alter the channel properties of NMDA receptors. Here we summarize recent advances in the characterization of NMDA receptor phosphorylation, emphasizing subunit-specific phosphorylation, which differentially controls the trafficking and surface expression of NMDA receptors.

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Figures

Figure 1
Figure 1
Phosphorylation sites on the cytosolic tails of NMDA receptor subunits. The cytosolic tails of NMDA receptor subunits NR1, NR2A, NR2B and NR2C contain about 100, 630, 640 and 400 amino acids, respectively. Each tail is phosphorylated on serine/threonine and/or tyrosine residues by a variety of kinases. Among identified phosphorylation sites: NR2A is uniquely phosphorylated by Cdk5; NR2B is uniquely phosphorylated by CKII; and NR2C is uniquely phosphorylated by PKB.
Figure 2
Figure 2
Differential regulation of NR2B-containing NMDA receptor trafficking by phosphorylation. Phosphorylation of NR2B on S1480 within the PDZ ligand by CKII disrupts the interaction between surface NMDA receptors and the PSD-95 family of proteins, causing internalization of surface-expressed NMDA receptors. However, phosphorylation of NR2B on Y1472 by Fyn kinase disrupts the interaction between NMDA receptors and the AP2-clathrin endocytic complex, leading to stabilization of the receptor on the cell surface. YEKL is a consensus AP-2 adaptor binding site, whereas ESDV is a consensus PDZ ligand.
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