Abstract
Proteins that bind to the cytoplasmic tails of AMPA receptors control receptor trafficking and thus the strength of postsynaptic responses. Here we show that AP2, a clathrin adaptor complex important for endocytosis, associates with a region of GluR2 that overlaps the NSF binding site. Peptides used previously to interfere with NSF binding also antagonize GluR2-AP2 interaction. Using GluR2 mutants and peptide variants that dissociate NSF and AP2 interaction, we find that AP2 is involved specifically in NMDA receptor-induced (but not ligand-dependent) internalization of AMPA receptors, and is essential for hippocampal long-term depression (LTD). NSF function, on the other hand, is needed to maintain synaptic AMPA receptor responses, but is not directly required for NMDA receptor-mediated internalization and LTD.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Protein Complex 2 / antagonists & inhibitors
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Adaptor Protein Complex 2 / metabolism*
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Animals
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Carrier Proteins / metabolism*
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Cell Membrane / drug effects
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Cell Membrane / metabolism
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Cell Membrane / ultrastructure
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Endocytosis / drug effects
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Endocytosis / physiology
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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 / genetics
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Hippocampus / cytology
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Hippocampus / drug effects
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Hippocampus / metabolism*
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Long-Term Synaptic Depression / drug effects
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Long-Term Synaptic Depression / physiology*
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N-Ethylmaleimide-Sensitive Proteins
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Neurons / cytology
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Neurons / drug effects
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Neurons / metabolism*
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Peptide Fragments / pharmacology
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Protein Transport / drug effects
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Protein Transport / physiology
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Rats
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Rats, Sprague-Dawley
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Receptors, AMPA / deficiency*
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Receptors, AMPA / drug effects
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Receptors, AMPA / genetics
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Synapses / drug effects
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Synapses / metabolism*
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Synapses / ultrastructure
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology
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Vesicular Transport Proteins*
Substances
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Adaptor Protein Complex 2
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Carrier Proteins
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Excitatory Amino Acid Agonists
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Peptide Fragments
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Receptors, AMPA
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Vesicular Transport Proteins
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N-Ethylmaleimide-Sensitive Proteins
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Nsf protein, rat
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glutamate receptor ionotropic, AMPA 2