Novel Anchorage of GluR2/3 to the Postsynaptic Density by the AMPA Receptor–Binding Protein ABP

• Published in: Neuron (Cambridge, Mass.) Mass.), 1998-09, Vol.21 (3), p.581-591
• Main Authors: Srivastava, S, Osten, P, Vilim, F.S, Khatri, L, Inman, G, States, B, Daly, C, DeSouza, S, Abagyan, R, Valtschanoff, J.G, Weinberg, R.J, Ziff, E.B
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Binding Sites; Brain - cytology; Brain - growth & development; Brain - metabolism; Carrier Proteins - chemistry; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cloning, Molecular; Gene Expression Regulation, Developmental; glutamic acid receptor-interacting proteins; Macromolecular Substances; Models, Molecular; Molecular Sequence Data; Nerve Tissue Proteins - chemistry; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Peptide Fragments - chemistry; postsynaptic density proteins; Protein Conformation; Rats; Receptors, AMPA - chemistry; Receptors, AMPA - metabolism; Recombinant Proteins - chemistry; Recombinant Proteins - metabolism; Sequence Alignment; Spinal Cord - cytology; Spinal Cord - growth & development; Spinal Cord - metabolism; Synapses - metabolism; Synapses - ultrastructure; Transcription, Genetic
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/S0896-6273(00)80568-1

We report the cloning of α-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.