PKA phosphorylation of AMPA receptor subunits controls synaptic trafficking underlying plasticity.
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.
Esteban
José A
JA
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA. estebanj@umich.edu
Shi
Song-Hai
SH
Wilson
Christopher
C
Nuriya
Mutsuo
M
Huganir
Richard L
RL
Malinow
Roberto
R
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*
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