Postsynaptic density-93 interacts with the δ2 glutamate receptor subunit at parallel fiber synapses

The glutamate receptor subunit delta 2 has a unique distribution at the parallel fiber-Purkinje cell synapse of the cerebellum, which is developmentally regulated such that delta 2 occurs at both parallel fiber synapses and climbing fiber synapses early in development but is restricted to parallel fiber synapses in adult animals. To identify proteins that might be involved in the trafficking or docking of delta 2 receptors, we screened a yeast two-hybrid library with the cytosolic C terminus of delta 2 and isolated a member of the postsynaptic density (PSD)-95 family of proteins, which are known to interact with the extreme C termini of NMDA receptors. We find that delta 2 binds specifically to PSD-93, which is enriched in Purkinje cells. In addition, PSD-93 clusters delta 2 when they are coexpressed in heterologous cells, and clustering is disrupted by point mutations of delta 2 that disrupt the delta 2-PSD-93 interaction. Ultrastructural localization of PSD-93 and delta 2 shows they are colocalized at parallel fiber synapses; however, PSD-93 also is present at climbing fiber synapses of the adult rat, where delta 2 is not found, indicating that the presence of PSD-93 alone is not sufficient for determining the synaptic expression of delta 2.