The amino-terminal domain of glutamate receptor δ2 triggers presynaptic differentiation

Glutamate receptor (GluR) δ2 selectively expressed in cerebellar Purkinje cells plays key roles in synapse formation, long-term depression and motor learning. We propose that GluRδ2 regulates synapse formation by making a physical linkage between the active zone and postsynaptic density. To examine the issue, GluRδ2-transfected 293T cells were cultured with cerebellar neurons. We found numerous punctate signals for presynaptic markers on the surface of 293T cells expressing GluRδ2. The presynaptic specializations induced by GluRδ2 were capable of exo- and endocytosis as indicated by FM1-43 dye labeling. Replacement of the extracellular N-terminal domain (NTD) of GluRδ2 with that of the AMPA receptor GluRα1 abolished the inducing activity. The NTD of GluRδ2 fused to the immunoglobulin constant region successfully induced the accumulation of presynaptic specializations on the surface of beads bearing the fusion protein. These results suggest that GluRδ2 triggers presynaptic differentiation by direct interaction with presynaptic components through the NTD.