CaMKII-dependent phosphorylation of GluK5 mediates plasticity of kainate receptors.
EMBO J
; 32(4): 496-510, 2013 Feb 20.
Article
in En
| MEDLINE
| ID: mdl-23288040
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Synapses
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Receptors, Kainic Acid
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Mossy Fibers, Hippocampal
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Calcium Signaling
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
Limits:
Animals
/
Humans
Language:
En
Journal:
EMBO J
Year:
2013
Document type:
Article
Affiliation country: