Abstract
Redistribution of postsynaptic AMPA- (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid-) subtype glutamate receptors may regulate synaptic strength at glutamatergic synapses, but the mediation of the redistribution is poorly understood. We show that AMPA receptors underwent clathrin-dependent endocytosis, which was accelerated by insulin in a GluR2 subunit-dependent manner. Insulin-stimulated endocytosis rapidly decreased AMPA receptor numbers in the plasma membrane, resulting in long-term depression (LTD) of AMPA receptor-mediated synaptic transmission in hippocampal CA1 neurons. Moreover, insulin-induced LTD and low-frequency stimulation-(LFS-) induced homosynaptic CA1 LTD were found to be mutually occlusive and were both blocked by inhibiting postsynaptic clathrin-mediated endocytosis. Thus, controlling postsynaptic receptor numbers through endocytosis may be an important mechanism underlying synaptic plasticity in the mammalian CNS.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Protein Complex alpha Subunits
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Adaptor Proteins, Vesicular Transport
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Animals
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Cell Line
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Clathrin / physiology*
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Coated Pits, Cell-Membrane / physiology
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Endocytosis / drug effects
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Endocytosis / physiology*
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Excitatory Postsynaptic Potentials / drug effects
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Excitatory Postsynaptic Potentials / physiology
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Hippocampus / chemistry
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Hippocampus / cytology
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Hippocampus / metabolism
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Humans
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Hypoglycemic Agents / pharmacology
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Insulin / pharmacology
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Kidney / cytology
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Long-Term Potentiation / drug effects
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Long-Term Potentiation / physiology
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Male
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Membrane Proteins / metabolism
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Neural Inhibition / drug effects
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Neural Inhibition / physiology
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Neuronal Plasticity / physiology
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Neurons / chemistry
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Neurons / cytology*
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Neurons / metabolism*
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Protein Structure, Tertiary
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Rats
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Rats, Sprague-Dawley
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Receptors, AMPA / chemistry
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Receptors, AMPA / metabolism*
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Receptors, Cell Surface / metabolism
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Synapses / chemistry
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Synapses / metabolism
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology*
Substances
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Adaptor Protein Complex alpha Subunits
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Adaptor Proteins, Vesicular Transport
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Clathrin
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Hypoglycemic Agents
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Insulin
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Membrane Proteins
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Receptors, AMPA
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Receptors, Cell Surface
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glutamate receptor ionotropic, AMPA 2