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CaMKII-dependent phosphorylation of GluK5 mediates plasticity of kainate receptors.
Carta, Mario; Opazo, Patrizio; Veran, Julien; Athané, Axel; Choquet, Daniel; Coussen, Françoise; Mulle, Christophe.
Afiliación
  • Carta M; Université Bordeaux, Institut Interdisciplinaire de Neurosciences, UMR 5297, Bordeaux, France.
EMBO J ; 32(4): 496-510, 2013 Feb 20.
Article en En | MEDLINE | ID: mdl-23288040
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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sinapsis / Receptores de Ácido Kaínico / Fibras Musgosas del Hipocampo / Señalización del Calcio / Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina Límite: Animals / Humans Idioma: En Revista: EMBO J Año: 2013 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sinapsis / Receptores de Ácido Kaínico / Fibras Musgosas del Hipocampo / Señalización del Calcio / Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina Límite: Animals / Humans Idioma: En Revista: EMBO J Año: 2013 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Reino Unido