Domain Interaction Between NMDA Receptor Subunits and the Postsynaptic Density Protein PSD-95

TLDR

The N‑methyl‑D‑aspartate (NMDA) receptor mediates synaptic glutamate‑induced transmission and plasticity in central neurons, and its interaction with PSD‑95 may influence the plasticity of excitatory synapses. Using a yeast two‑hybrid system, the authors demonstrated that the cytoplasmic tails of NMDA receptor subunits bind PSD‑95, with the second PDZ domain of PSD‑95 recognizing the seven‑amino‑acid COOH‑terminal tSXV motif present in NR2 subunits and certain NR1 splice forms. Transcripts encoding PSD‑95 are expressed in a pattern similar to NMDA receptors, and the NR2B subunit co‑localizes with PSD‑95 in cultured rat hippocampal neurons.

Abstract

The N -methyl-D-aspartate (NMDA) receptor subserves synaptic glutamate-induced transmission and plasticity in central neurons. The yeast two-hybrid system was used to show that the cytoplasmic tails of NMDA receptor subunits interact with a prominent postsynaptic density protein PSD-95. The second PDZ domain in PSD-95 binds to the seven-amino acid, COOH-terminal domain containing the terminal t SXV motif (where S is serine, X is any amino acid, and V is valine) common to NR2 subunits and certain NR1 splice forms. Transcripts encoding PSD-95 are expressed in a pattern similar to that of NMDA receptors, and the NR2B subunit co-localizes with PSD-95 in cultured rat hippocampal neurons. The interaction of these proteins may affect the plasticity of excitatory synapses.