Role of the carboxy-terminal region of the GluRε2 subunit in synaptic localization of the NMDA receptor channel

The synaptic localization of the N-methyl-D-aspartate (NMDA) type glutamate receptor (GluR) channel is a prerequisite for synaptic plasticity in the brain. We generated mutant mice carrying the carboxy-terminal truncated GluR epsilon 2 subunit of the NMDA receptor channel. The mutant mice died neonatally and failed to form barrelette structures in the brainstem. The mutation greatly decreased the NMDA receptor-mediated component of hippocampal excitatory postsynaptic potentials and punctate immunofluorescent labelings of GluR epsilon 2 protein in the neuropil regions, while GluR epsilon 2 protein expression was comparable. Immunostaining of cultured cerebral neurons showed the reduced punctate staining of the truncated GluR epsilon 2 protein at synapses. These results suggest that the carboxy-terminal region of the GluR epsilon 2 subunit is important for efficient clustering and synaptic localization of the NMDA receptor channel.