Synapse-associated proteins (SAPs) are constituents of the pre- and po
stsynaptic submembraneous cytomatrix. Here, we present SAP102, a novel
102 kDa SAP detected in dendritic shafts and spines of asymmetric typ
e 1 synapses. SAP102 is enriched in preparations of synaptic junctions
, where it biochemically behaves as a component of the cortical cytosk
eleton. Antibodies directed against NMDA receptors coimmunoprecipitate
SAP102 from rat brain synaptosomes. Recombinant proteins containing t
he carboxy-terminal tail of NMDA receptor subunit NR2B interact with S
AP102 from rat brain homogenates. All three PDZ domains in SAP102 bind
the cytoplasmic tail of NR2B in vitro. These data represent direct ev
idence that in vivo SAP102 is involved in linking NMDA receptors to th
e submembraneous cytomatrix associated with postsynaptic densities at
excitatory synapses.