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

Antonio Sanz-Clemente, John Gray, Kyle A. Ogilvie, Roger A. Nicoll, Katherine W. Roche

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)607-614
Number of pages8
JournalCell Reports
Volume3
Issue number3
DOIs
StatePublished - 2013
Externally publishedYes

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Casein Kinase II
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Neurotransmitter Receptor
N-Methyl-D-Aspartate Receptors
Synapses
Phosphorylation
Calcium
Chemical analysis
Phosphotransferases
Display devices
Association reactions
Ligands

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Activated CaMKII Couples GluN2B and Casein Kinase 2 to Control Synaptic NMDA Receptors. / Sanz-Clemente, Antonio; Gray, John; Ogilvie, Kyle A.; Nicoll, Roger A.; Roche, Katherine W.

In: Cell Reports, Vol. 3, No. 3, 2013, p. 607-614.

Research output: Contribution to journalArticle

Sanz-Clemente, Antonio ; Gray, John ; Ogilvie, Kyle A. ; Nicoll, Roger A. ; Roche, Katherine W. / Activated CaMKII Couples GluN2B and Casein Kinase 2 to Control Synaptic NMDA Receptors. In: Cell Reports. 2013 ; Vol. 3, No. 3. pp. 607-614.
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