CaMKII triggers the diffusional trapping of surface AMPARs through phosphorylation of stargazin.
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.
Opazo
Patricio
P
CNRS UMR 5091, Cellular Physiology of the Synapse, Bordeaux, France.
Labrecque
Simon
S
Tigaret
Cezar M
CM
Frouin
Arnaud
A
Wiseman
Paul W
PW
De Koninck
Paul
P
Choquet
Daniel
D
D000200:Action Potentials / Q000187:drug effects / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D001581:Benzothiadiazines / Q000494:pharmacology; D001596:Benzylamines / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D002478:Cells, Cultured; D004058:Diffusion; D000076122:Disks Large Homolog 4 Protein; D004558:Electric Stimulation / Q000379:methods; D004622:Embryo, Mammalian; D004789:Enzyme Activation / Q000187:drug effects; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000166:cytology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008954:Models, Biological; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018709:Statistics, Nonparametric; D013449:Sulfonamides / Q000494:pharmacology; D014162:Transfection / Q000379:methods; D000096926:Benzenesulfonamides
D001581:Benzothiadiazines; D001596:Benzylamines; D002118:Calcium; D015220:Calcium Channels; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D000076122:Disks Large Homolog 4 Protein; D049452:Green Fluorescent Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D047428:Protein Kinase Inhibitors; D018091:Receptors, AMPA; D013449:Sulfonamides; C491911:Cacng2 protein, rat; C501449:Dlg4 protein, rat; C072105:KN 93; D000096926:Benzenesulfonamides; C004639:cyclothiazide