Glutamate Receptor Anchoring Proteins and the Molecular Organization of Excitatory Synapses

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Abstract
Ionotropic glutamate receptors are concentrated at postsynaptic sites in excitatory synapses. The cytoplasmic C‐terminal tail of certain glutamate receptor subunits interact with specific PDZ domain‐containing proteins. NMDA receptor NR2 subunits bind to the PSD‐95 family of proteins, whereas AMPA receptor subunits GluR2/3 bind to GRIP. These interactions may underlie the clustering, targeting, and immobilization of the glutamate receptors at postsynaptic sites. By virtue of their multiple protein‐binding domains (e.g., three PDZs in PSD‐95 and seven PDZs in GRIP), PSD‐95 and GRIP can function as multivalent proteins that organize a specific cytoskeletal and signaling complex associated with each class of glutamate receptor. The network of protein‐protein interactions mediated by these abundant PDZ proteins is likely to contribute significantly to the molecular scaffold of the postsynaptic density.