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Activated CaMKII Couples GluN2B and Casein Kinase 2 to Control Synaptic NMDA Receptors
Journal article   Open access   Peer reviewed

Activated CaMKII Couples GluN2B and Casein Kinase 2 to Control Synaptic NMDA Receptors

Antonio Sanz-Clemente, John A. Gray, Kyle A. Ogilvie, Roger A. Nicoll and Katherine W. Roche
Cell reports (Cambridge), v 3(3), pp 607-614
01 Mar 2013
PMID: 23478024
url
http://www.cell.com/article/S2211124713000703/pdfView
Published, Version of Record (VoR) Open
url
https://doi.org/10.1016/j.celrep.2013.02.011View
Published, Version of Record (VoR) Open

Abstract

Cell Biology Life Sciences & Biomedicine Science & Technology
Synaptic activity triggers a profound reorganization of the molecular composition of excitatory synapses. For example, NMDA receptors are removed from synapses in an activity- and calcium-dependent manner, via casein kinase 2 (CK2) phosphorylation of the PDZ ligand of the GluN2B subunit (S1480). However, how synaptic activity drives this process remains unclear because CK2 is a constitutively active kinase, which is not directly regulated by calcium. We show here that activated CaMKII couples GluN2B and CK2 to form a trimolecular complex and increases CK2-mediated phosphorylation of GluN2B S1480. In addition, a GluN2B mutant, which contains an insert to mimic the GluN2A sequence and cannot bind to CaMKII, displays reduced S1480 phosphorylation and increased surface expression. We find that although disrupting GluN2B/CaMKII binding reduces synapse number, it increases synaptic-GluN2B content. Therefore, the GluN2B/CaMKII association controls synapse density and PSD composition in an activity-dependent manner, including recruitment of CK2 for the removal of GluN2B from synapses.

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Cell Biology
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