Identification of a juxtamembrane segment of the glutamate receptor delta2 subunit required for the plasma membrane localization

Glutamate receptor delta2 subunit (GluRdelta2) is selectively expressed in cerebellar Purkinje cells and is specifically targeted to parallel fiber synapses, where GluRdelta2 plays important roles in synaptic plasticity, motor learning and synapse formation. Here, we investigated the mechanism of GluRdelta2 sorting using MDCK epithelial cells. Immunocytochemical analysis of subcellular localization showed that GluRdelta2 expressed in MDCK cells was predominantly distributed in the plasma membrane. By examining the subcellular localization of GluRdelta2 mutants with various deletions in the carboxyl-terminal cytoplasmic region, we identified J segment adjacent to transmembrane segment M4 as a key region for the efficient targeting of GluRdelta2 to the plasma membrane. On the other hand, the carboxyl terminus of GluRdelta2 essential for interaction with PDZ domain proteins was dispensable for the plasma membrane localization. Our results suggest that the juxtamembrane segment and the PDZ domain target site at the carboxyl terminus of GluRdelta2 play differential roles in plasma membrane targeting, synapse localization and signal transduction.