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Volume 17, Number 19,
Issue of October 1, 1997
pp. 7351-7358
Copyright ©1997 Society for Neuroscience
Redistribution and Stabilization of Cell Surface Glutamate
Receptors during Synapse Formation
Andrew L. Mammen1, 2,
Richard L. Huganir1, 2, and
Richard J. O'Brien1, 2, 3
1 Howard Hughes Medical Institute, and Departments of
2 Neuroscience and 3 Neurology, Johns Hopkins
University School of Medicine, Baltimore, Maryland 21205
Although the regulation of neurotransmitter receptors during
synaptogenesis has been studied extensively at the neuromuscular junction, little 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-GluR1) domains of the AMPA receptor subunit
GluR1, combined with surface biotinylation and metabolic labeling
studies, we have characterized the redistribution and metabolic
stabilization of the AMPA receptor subunit GluR1 during synapse
formation in culture. Before synapse formation, GluR1 is distributed
widely, both on the surface and within the dendritic cytoplasm of these neurons. The diffuse cell surface pool of receptor appears to be mobile
within the membrane and can be induced to cluster by the addition of
N-GluR1 to live neurons. As cultures mature and synapses form, there is
a redistribution of surface GluR1 into clusters 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 pool of GluR1 that is present
on the cell surface. Blockade of postsynaptic AMPA and NMDA receptors
had no effect on the redistribution of GluR1. These results begin to
characterize the events regulating the distribution of AMPA receptors
and demonstrate similarities between synapse formation at the
neuromuscular junction and at excitatory synapses in cultured
neurons.
Key words:
GluR1;
synaptogenesis;
spinal cord;
metabolism;
glutamate
receptors;
rat;
tissue culture
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