SAP102, a Novel Postsynaptic Protein That Interacts with NMDA Receptor Complexes In Vivo

TLDR

Synapse‑associated proteins are key components of the pre‑ and postsynaptic cytomatrix, and SAP102 is enriched in synaptic junctions where it behaves as a cortical cytoskeletal element. The study introduces SAP102, a novel 102‑kDa postsynaptic protein localized to dendritic shafts and spines of asymmetric type 1 synapses. Co‑immunoprecipitation and recombinant tail‑binding assays demonstrate that SAP102 associates with the NR2B subunit of NMDA receptors through its PDZ domains. These results provide direct evidence that SAP102 links NMDA receptors to the postsynaptic submembranous cytomatrix at excitatory synapses.

Abstract

Synapse-associated proteins (SAPs) are constituents of the pre- and postsynaptic submembraneous cytomatrix. Here, we present SAP102, a novel 102 kDa SAP detected in dendritic shafts and spines of asymmetric type 1 synapses. SAP102 is enriched in preparations of synaptic junctions, where it biochemically behaves as a component of the cortical cytoskeleton. Antibodies directed against NMDA receptors coimmunoprecipitate SAP102 from rat brain synaptosomes. Recombinant proteins containing the carboxy-terminal tail of NMDA receptor subunit NR2B interact with SAP102 from rat brain homogenates. All three PDZ domains in SAP102 bind the cytoplasmic tail of NR2B in vitro. These data represent direct evidence that in vivo SAP102 is involved in linking NMDA receptors to the submembraneous cytomatrix associated with postsynaptic densities at excitatory synapses.