Abstract
We report the cloning of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor-binding protein (ABP), a postsynaptic density (PSD) protein related to glutamate receptor-interacting protein (GRIP) with two sets of three PDZ domains, which binds the GluR2/3 AMPA receptor subunits. ABP exhibits widespread CNS expression and is found at the postsynaptic membrane. We show that the protein interactions of the ABP/GRIP family differ from the PSD-95 family, which binds N-methyl-D-aspartate (NMDA) receptors. ABP binds to the GluR2/3 C-terminal VKI-COOH motif via class II hydrophobic PDZ interactions, distinct from the class I PSD-95-NMDA receptor interaction. ABP and GRIP also form homo- and heteromultimers through PDZ-PDZ interactions but do not bind PSD-95. We suggest that the ABP/GRIP and PSD-95 families form distinct scaffolds that anchor, respectively, AMPA and NMDA receptors.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Binding Sites
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Brain / cytology
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Brain / growth & development
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Brain / metabolism*
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Carrier Proteins / chemistry
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cloning, Molecular
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Gene Expression Regulation, Developmental
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Intercellular Signaling Peptides and Proteins
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Intracellular Signaling Peptides and Proteins
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Macromolecular Substances
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Models, Molecular
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Molecular Sequence Data
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Nerve Tissue Proteins / chemistry
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Peptide Fragments / chemistry
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Protein Conformation
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Rats
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Receptors, AMPA / chemistry*
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Receptors, AMPA / metabolism*
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Recombinant Proteins / chemistry
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Recombinant Proteins / metabolism
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Sequence Alignment
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Spinal Cord / cytology
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Spinal Cord / growth & development
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Spinal Cord / metabolism*
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Synapses / metabolism*
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Synapses / ultrastructure
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Transcription, Genetic
Substances
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Carrier Proteins
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Grip1 protein, rat
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Grip2 protein, rat
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Intercellular Signaling Peptides and Proteins
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Intracellular Signaling Peptides and Proteins
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Macromolecular Substances
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Nerve Tissue Proteins
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Peptide Fragments
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Receptors, AMPA
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Recombinant Proteins
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glutamate receptor ionotropic, AMPA 3
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glutamate receptor ionotropic, AMPA 2