Abstract
The endocytosis of AMPA receptors is thought to be important in the expression of long-term depression (LTD) triggered by NMDA receptor activation. Although signaling pathways necessary for LTD induction have been identified, those responsible for the regulated internalization of AMPA receptors are unknown. Here we show that activation of NMDA receptors alone can trigger AMPA receptor endocytosis through calcium influx and activation of the calcium-dependent protein phosphatase calcineurin. A distinct signaling mechanism mediates the AMPA receptor endocytosis stimulated by insulin. These results demonstrate that although multiple signaling pathways can induce AMPA receptor internalization, NMDA receptor activation enhances AMPA receptor endocytosis via a signaling mechanism required for the induction of LTD.
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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Animals
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Animals, Newborn
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Calcineurin / drug effects
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Calcineurin / metabolism
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Calcium Signaling / drug effects
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Calcium Signaling / physiology
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Cell Compartmentation / drug effects
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Cell Compartmentation / physiology
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Cells, Cultured
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Dendrites / drug effects
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Dendrites / metabolism
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Dendrites / ultrastructure
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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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N-Methylaspartate / pharmacology
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Neural Inhibition / drug effects
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Neural Inhibition / physiology*
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Neurons / drug effects
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Neurons / metabolism*
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Neurons / ultrastructure
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Rats
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Receptors, AMPA / drug effects
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Receptors, AMPA / metabolism*
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Receptors, N-Methyl-D-Aspartate / drug effects
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Receptors, N-Methyl-D-Aspartate / metabolism
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology
Substances
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Receptors, AMPA
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Receptors, N-Methyl-D-Aspartate
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N-Methylaspartate
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
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Calcineurin