Glutamate Receptor Anchoring Proteins and the Molecular Organization of Excitatory Synapses

Authors

  • MORGAN SHENG,

    Corresponding author
    1. Howard Hughes Medical Institute and Department of Neurobiology, Massachussets General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA
      Corresponding author: Morgan Sheng, HHMI (Wellman 423), Massachusetts General Hospital, 50 Blossom Street, Boston, MA 02114. Phone: 617–724–2800; fax: 617–724–2805; e-mail: sheng@helix.mgh.harvard.edu
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  • DANIEL T. PAK

    1. Howard Hughes Medical Institute and Department of Neurobiology, Massachussets General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA
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Corresponding author: Morgan Sheng, HHMI (Wellman 423), Massachusetts General Hospital, 50 Blossom Street, Boston, MA 02114. Phone: 617–724–2800; fax: 617–724–2805; e-mail: sheng@helix.mgh.harvard.edu

Abstract

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.

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