Abstract
Here, we show that N-ethylmaleimide-sensitive fusion protein (NSF) interacts directly and selectively with the intracellular C-terminal domain of the GluR2 subunit of AMPA receptors. The interaction requires all three domains of NSF but occurs between residues Lys-844 and Gln-853 of rat GluR2, with Asn-851 playing a critical role. Loading of decapeptides corresponding to the NSF-binding domain of GluR2 into rat hippocampal CA1 pyramidal neurons results in a marked, progressive decrement of AMPA receptor-mediated synaptic transmission. This reduction in synaptic transmission was also observed when an anti-NSF monoclonal antibody (mAb) was loaded into CA1 neurons. These results demonstrate a previously unsuspected direct interaction in the postsynaptic neuron between two major proteins involved in synaptic transmission and suggest a rapid NSF-dependent modulation of AMPA receptor function.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Antibodies, Monoclonal / immunology
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Antibodies, Monoclonal / pharmacology
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Carrier Proteins / immunology
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Carrier Proteins / metabolism
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Cells, Cultured
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Excitatory Amino Acid Agonists / pharmacology
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Excitatory Postsynaptic Potentials / drug effects
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Excitatory Postsynaptic Potentials / physiology
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Hippocampus / drug effects
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Hippocampus / metabolism
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Hippocampus / physiology
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Molecular Sequence Data
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N-Ethylmaleimide-Sensitive Proteins
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Neurons / drug effects
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Rats
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Rats, Wistar
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Receptors, AMPA / physiology
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Receptors, Glutamate / genetics
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Receptors, Glutamate / metabolism*
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Synaptic Transmission / physiology*
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Vesicular Transport Proteins*
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology
Substances
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Antibodies, Monoclonal
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Carrier Proteins
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Excitatory Amino Acid Agonists
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Receptors, AMPA
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Receptors, Glutamate
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Vesicular Transport Proteins
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
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N-Ethylmaleimide-Sensitive Proteins
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Nsf protein, rat