ROLE OF THE CARBOXY-TERMINAL REGION OF THE GLUR-EPSILON-2 SUBUNIT IN SYNAPTIC LOCALIZATION OF THE NMDA RECEPTOR-CHANNEL

The synaptic localization of the N-methyl-D-aspartate (NMDA) type glut amate receptor (GluR) channel is a prerequisite for synaptic plasticit y in the brain. We generated mutant mice carrying the carboxy-terminal truncated GluR epsilon 2 subunit of the NMDA receptor channel. The mu tant mice died neonatally and failed to form barrelette structures in the brainstem. The mutation greatly decreased the NMDA receptor-mediat ed component of hippocampal excitatory postsynaptic potentials and pun ctate immunofluorescent labelings of GluR epsilon 2 protein in the neu ropil regions, while GluR epsilon 2 protein expression was comparable. Immunostaining of cultured cerebral neurons showed the reduced puncta te 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 localizat ion of the NMDA receptor channel.