Abstract
The Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is critically required for the synaptic recruitment of AMPA-type glutamate receptors (AMPARs) during both development and plasticity. However, the underlying mechanism is unknown. Using single-particle tracking of AMPARs, we show that CaMKII activation and postsynaptic translocation induce the synaptic trapping of AMPARs diffusing in the membrane. AMPAR immobilization requires both phosphorylation of the auxiliary subunit Stargazin and its binding to PDZ domain scaffolds. It does not depend on the PDZ binding domain of GluA1 AMPAR subunit nor its phosphorylation at Ser831. Finally, CaMKII-dependent AMPAR immobilization regulates short-term plasticity. Thus, NMDA-dependent Ca(2+) influx in the post-synapse triggers a CaMKII- and Stargazin-dependent decrease in AMPAR diffusional exchange at synapses that controls synaptic function.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Action Potentials / drug effects
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Action Potentials / genetics
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Animals
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Animals, Newborn
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Benzothiadiazines / pharmacology
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Benzylamines / pharmacology
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Calcium / metabolism
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Calcium Channels / metabolism*
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Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism*
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Cells, Cultured
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Diffusion
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Disks Large Homolog 4 Protein
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Electric Stimulation / methods
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Embryo, Mammalian
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Enzyme Activation / drug effects
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Excitatory Postsynaptic Potentials / drug effects
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Excitatory Postsynaptic Potentials / genetics
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Green Fluorescent Proteins / genetics
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Hippocampus / cytology
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Intracellular Signaling Peptides and Proteins / metabolism
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Membrane Proteins / metabolism
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Models, Biological
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Neurons / drug effects
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Neurons / metabolism*
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Phosphorylation / drug effects
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Phosphorylation / physiology
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Protein Kinase Inhibitors / pharmacology
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Protein Transport
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Rats
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Rats, Sprague-Dawley
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Receptors, AMPA / antagonists & inhibitors
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Receptors, AMPA / genetics
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Receptors, AMPA / metabolism*
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Statistics, Nonparametric
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Sulfonamides / pharmacology
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Transfection / methods
Substances
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Benzothiadiazines
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Benzylamines
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Cacng2 protein, rat
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Calcium Channels
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Disks Large Homolog 4 Protein
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Dlg4 protein, rat
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Protein Kinase Inhibitors
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Receptors, AMPA
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Sulfonamides
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KN 93
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Green Fluorescent Proteins
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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cyclothiazide
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Calcium