title: CaMKII-dependent phosphorylation of GluK5 mediates plasticity of kainate receptors.
abstract: Calmodulin-dependent kinase II (CaMKII) is key for long-term potentiation of synaptic AMPA receptors. Whether CaMKII is involved in activity-dependent plasticity of other ionotropic glutamate receptors is unknown. We show that repeated pairing of pre- and postsynaptic stimulation at hippocampal mossy fibre synapses induces long-term depression of kainate receptor (KAR)-mediated responses, which depends on Ca(2+) influx, activation of CaMKII, and on the GluK5 subunit of KARs. CaMKII phosphorylation of three residues in the C-terminal domain of GluK5 subunit markedly increases lateral mobility of KARs, possibly by decreasing the binding of GluK5 to PSD-95. CaMKII activation also promotes surface expression of KARs at extrasynaptic sites, but concomitantly decreases its synaptic content. Using a molecular replacement strategy, we demonstrate that the direct phosphorylation of GluK5 by CaMKII is necessary for KAR-LTD. We propose that CaMKII-dependent phosphorylation of GluK5 is responsible for synaptic depression by untrapping of KARs from the PSD and increased diffusion away from synaptic sites.
authors.affiliation: Université Bordeaux, Institut Interdisciplinaire de Neurosciences, UMR 5297, Bordeaux, France.
authors.forename: Mario
authors.initials: M
authors.lastname: Carta
authors.forename: Patrizio
authors.initials: P
authors.lastname: Opazo
authors.forename: Julien
authors.initials: J
authors.lastname: Veran
authors.forename: Axel
authors.initials: A
authors.lastname: Athané
authors.forename: Daniel
authors.initials: D
authors.lastname: Choquet
authors.forename: Françoise
authors.initials: F
authors.lastname: Coussen
authors.forename: Christophe
authors.initials: C
authors.lastname: Mulle
mesh_terms: D000818:Animals; D019556:COS Cells; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism*; D002522:Chlorocebus aethiops; D000076122:Disks Large Homolog 4 Protein; D051528:Guanylate Kinases / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D019599:Mossy Fibers, Hippocampal / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D051381:Rats; D018092:Kainic Acid Receptors / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000235:genetics / Q000378:metabolism*
chemical_list: D002118:Calcium; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D000076122:Disks Large Homolog 4 Protein; D051528:Guanylate Kinases; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D018092:Kainic Acid Receptors; C501444:DLG4 protein, human; C501447:Dlg4 protein, mouse; C501449:Dlg4 protein, rat