Abstract
The regulated incorporation of AMPA receptors into synapses is important for synaptic plasticity. Here we examine the role of protein kinase A (PKA) in this process. We found that PKA phosphorylation of the AMPA receptor subunits GluR4 and GluR1 directly controlled the synaptic incorporation of AMPA receptors in organotypic slices from rat hippocampus. Activity-driven PKA phosphorylation of GluR4 was necessary and sufficient to relieve a retention interaction and drive receptors into synapses. In contrast, PKA phosphorylation of GluR1 and the activity of calcium/calmodulin-dependent kinase II (CaMKII) were both necessary for receptor incorporation. Thus, PKA phosphorylation of AMPA receptor subunits contributes to diverse mechanisms underlying synaptic plasticity.
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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Amino Acid Sequence / physiology
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Animals
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Animals, Newborn
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Cyclic AMP / metabolism
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Cyclic AMP / pharmacology
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Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
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Cyclic AMP-Dependent Protein Kinases / metabolism*
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Excitatory Postsynaptic Potentials / drug effects
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Excitatory Postsynaptic Potentials / physiology
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Hippocampus / cytology
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Hippocampus / enzymology*
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Mutation / genetics
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Neuronal Plasticity / physiology*
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Phosphorylation
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Presynaptic Terminals / enzymology*
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Presynaptic Terminals / ultrastructure
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Protein Transport / physiology*
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Rats
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Receptors, AMPA / genetics
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Receptors, AMPA / metabolism*
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Serine / metabolism
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Synaptic Transmission / physiology*
Substances
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Receptors, AMPA
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glutamate receptor ionotropic, AMPA 4
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Serine
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Cyclic AMP
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Cyclic AMP-Dependent Protein Kinases
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Calcium-Calmodulin-Dependent Protein Kinases
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glutamate receptor ionotropic, AMPA 1