CaMKII-dependent phosphorylation of GluK5 mediates plasticity of kainate receptors.
EMBO J. 2013-01-04; 32(4): 496-510
DOI: 10.1038/emboj.2012.334
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1. EMBO J. 2013 Feb 20;32(4):496-510. doi: 10.1038/emboj.2012.334. Epub 2013 Jan 4.
CaMKII-dependent phosphorylation of GluK5 mediates plasticity of kainate
receptors.
Carta M(1), Opazo P, Veran J, Athané A, Choquet D, Coussen F, Mulle C.
Author information:
(1)Université Bordeaux, Institut Interdisciplinaire de Neurosciences, UMR 5297,
Bordeaux, France.
Comment in
EMBO J. 2013 Feb 20;32(4):487-9.
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.
DOI: 10.1038/emboj.2012.334
PMCID: PMC3579137
PMID: 23288040 [Indexed for MEDLINE]