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

Abstract

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.