A developmental change in NMDA receptor-associated proteins at hippocampalsynapses

The membrane-associated guanylate kinases [Chapsyn-110/postsynaptic density -93 (PSD-93), synapse-associated protein-90 (SAP-90)/PSD-95, and SAP-102] a re believed to cluster and anchor NMDA receptors at the synapse and to play a role in signal transduction. We have investigated the developmental chan ges in expression of these proteins in rat hippocampus using biochemical an alyses and quantitative immunogold electron microscopy. At postnatal day 2 (P2), SAP-102 was highly expressed, whereas PSD-93 and PSD-95 were low. SAP -102 expression increased during the first week, stayed stable through P35, and showed a reduced expression at 6 months. From P2 through 6 months, PSD -93 and PSD-95 increased. For PSD-95, the percent of labeled synapses incre ased almost threefold with age, whereas the number of gold particles per la beled synapse did not change significantly, suggesting that the increase in PSD-95 is attributable primarily to an increase in the number of synapses containing PSD-95. In contrast, for SAP-102, both percent labeled synapses and the number of gold particles per labeled synapse decreased during this time. From Western blots of hippocampus and immunogold analysis of CA1 syna pses, the high expression of NR2B at P2 coincides with the high level of SA P-102 at synapses, whereas the later expression of NR2A coincides with that of PSD-93 and PSD-95. To determine whether the changes in PSD-93/95 and SA P-102 reflect preferred associations with NR2A and NR2B, respectively, we m easured co-immunoprecipitation in the adult hippocampus. These studies sugg est that there is a preference for complexes of NR2A/PSD-93/95 and NR2B/SAP -102. These results indicate that individual receptor-associated proteins m ay have specific functions that are critical to synapse development.