title: PKA phosphorylation of AMPA receptor subunits controls synaptic trafficking underlying plasticity.
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.
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA. estebanj@umich.edu
authors.forename: José A
authors.initials: JA
authors.lastname: Esteban
authors.forename: Song-Hai
authors.initials: SH
authors.lastname: Shi
authors.forename: Christopher
authors.initials: C
authors.lastname: Wilson
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Nuriya
authors.forename: Richard L
authors.initials: RL
authors.lastname: Huganir
authors.forename: Roberto
authors.initials: R
authors.lastname: Malinow
mesh_terms: D000595:Amino Acid Sequence / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000201:enzymology*; D009154:Mutation / Q000235:genetics; D009473:Neuronal Plasticity / Q000502:physiology*; D010766:Phosphorylation; D017729:Presynaptic Terminals / Q000201:enzymology* / Q000648:ultrastructure; D021381:Protein Transport / Q000502:physiology*; D051381:Rats; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D018091:Receptors, AMPA; D012694:Serine; C104724:glutamate receptor ionotropic, AMPA 4