Glutamate receptor anchoring proteins and the molecular organization of excitatory synapses.
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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Howard Hughes Medical Institute, Massachussets General Hospital, Boston 02114, USA. sheng@helix.mgh.harvard.edu
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D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry; D003599:Cytoskeleton / Q000737:chemistry; D004330:Drosophila; D029721:Drosophila Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D018091:Receptors, AMPA / Q000378:metabolism; D017470:Receptors, Glutamate / Q000737:chemistry*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D015398:Signal Transduction; D013569:Synapses / Q000378:metabolism*
D002352:Carrier Proteins; D029721:Drosophila Proteins; C491307:Grip protein, Drosophila; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C033652:postsynaptic density proteins