REDISTRIBUTION AND STABILIZATION OF CELL-SURFACE GLUTAMATE RECEPTORS DURING SYNAPSE FORMATION

Although the regulation of neurotransmitter receptors during synaptoge nesis has been studied extensively at the neuromuscular junction, litt le is known about the control of excitatory neurotransmitter receptors during synapse formation in central neurons. Using antibodies against extracellular N-terminal (N-GluR1) and intracellular C-terminal (C-Gl uR1) domains of the AMPA receptor subunit GluR1, combined with surface biotinylation and metabolic labeling studies, we have characterized t he redistribution and metabolic stabilization of the AMPA receptor sub unit GluR1 during synapse formation in culture. Before synapse formati on, GluR1 is distributed widely, both on the surface and within the de ndritic cytoplasm of these neurons. The diffuse cell surface pool of r eceptor appears to be mobile within the membrane and can be induced to cluster by the addition of N-GluR1 to live neurons. As cultures matur e and synapses form, there is a redistribution of surface GluR1 into c lusters at excitatory synapses where it appears to be immobilized. The change in the distribution of GluR1 is accompanied by an increase in both the half-life of the receptor and the percentage of the total poo l of GluR1 that is present on the cell surface. Blockade of postsynapt ic AMPA and NMDA receptors had no effect on the redistribution of GluR 1. These results begin to characterize the events regulating the distr ibution of AMPA receptors and demonstrate similarities between synapse formation at the neuromuscular junction and at excitatory synapses in cultured neurons.