Abstract
Here, we show that disruption of N-ethylmaleimide-sensitive fusion protein- (NSF-) GluR2 interaction by infusion into cultured hippocampal neurons of a blocking peptide (pep2m) caused a rapid decrease in the frequency but no change in the amplitude of AMPA receptor-mediated miniature excitatory postsynaptic currents (mEPSCs). N-methyl-D-aspartate (NMDA) receptor-mediated mEPSCs were not changed. Viral expression of pep2m reduced the surface expression of alpha-amino-3-hydroxy-5-methyl-isoxazolepropionate (AMPA) receptors, whereas NMDA receptor surface expression in the same living cells was unchanged. In permeabilized neurons, the total amount of GluR2 immunoreactivity was unchanged, and a punctate distribution of GluR2 was observed throughout the dendritic tree. These data suggest that the NSF-GluR2 interaction is required for the surface expression of GluR2-containing AMPA receptors and that disruption of the interaction leads to the functional elimination of AMPA receptors at synapses.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenoviridae / genetics
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Animals
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Carrier Proteins / physiology*
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Cells, Cultured
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Electrophoresis, Polyacrylamide Gel
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Electrophysiology
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Excitatory Postsynaptic Potentials / physiology
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Hippocampus / cytology
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Hippocampus / metabolism*
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Hippocampus / ultrastructure
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Immunoblotting
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Immunohistochemistry
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N-Ethylmaleimide-Sensitive Proteins
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Neurons / metabolism*
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Neurons / ultrastructure
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Rats
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Receptors, AMPA / biosynthesis*
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Receptors, AMPA / metabolism
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Receptors, AMPA / physiology
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Receptors, N-Methyl-D-Aspartate / biosynthesis
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Receptors, N-Methyl-D-Aspartate / physiology
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Synaptic Membranes / physiology
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Synaptophysin / metabolism
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Transfection
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Vesicular Transport Proteins*
Substances
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Carrier Proteins
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Receptors, AMPA
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Receptors, N-Methyl-D-Aspartate
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Synaptophysin
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Vesicular Transport Proteins
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glutamate receptor ionotropic, AMPA 4
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N-Ethylmaleimide-Sensitive Proteins
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Nsf protein, rat
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glutamate receptor ionotropic, AMPA 2
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glutamate receptor ionotropic, AMPA 1