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PMID:20670832

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Citation

Opazo, P, Labrecque, S, Tigaret, CM, Frouin, A, Wiseman, PW, De Koninck, P and Choquet, D (2010) CaMKII triggers the diffusional trapping of surface AMPARs through phosphorylation of stargazin. Neuron 67:239-52

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.

Links

PubMed Online version:10.1016/j.neuron.2010.06.007

Keywords

Action Potentials/drug effects; Action Potentials/genetics; Animals; Animals, Newborn; Benzothiadiazines/pharmacology; Benzylamines/pharmacology; Calcium/metabolism; Calcium Channels/metabolism; Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism; Cells, Cultured; Diffusion; Disks Large Homolog 4 Protein; Electric Stimulation/methods; Embryo, Mammalian; Enzyme Activation/drug effects; Excitatory Postsynaptic Potentials/drug effects; Excitatory Postsynaptic Potentials/genetics; Green Fluorescent Proteins/genetics; Hippocampus/cytology; Intracellular Signaling Peptides and Proteins/metabolism; Membrane Proteins/metabolism; Models, Biological; Neurons/drug effects; Neurons/metabolism; Phosphorylation/drug effects; Phosphorylation/physiology; Protein Kinase Inhibitors/pharmacology; Protein Transport; Rats; Rats, Sprague-Dawley; Receptors, AMPA/antagonists & inhibitors; Receptors, AMPA/genetics; Receptors, AMPA/metabolism; Statistics, Nonparametric; Sulfonamides/pharmacology; Transfection/methods

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:KCC2A

involved_in

GO:0098989: NMDA selective glutamate receptor signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:KCC2A

involved_in

GO:0099004: calmodulin dependent kinase signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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