title: Activated CaMKII couples GluN2B and casein kinase 2 to control synaptic NMDA receptors.
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.
authors.affiliation: Receptor Biology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: Sanz-Clemente
authors.forename: John A
authors.initials: JA
authors.lastname: Gray
authors.forename: Kyle A
authors.initials: KA
authors.lastname: Ogilvie
authors.forename: Roger A
authors.initials: RA
authors.lastname: Nicoll
authors.forename: Katherine W
authors.initials: KW
authors.lastname: Roche
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D047390:Casein Kinase II / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D011485:Protein Binding; D021381:Protein Transport; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*
chemical_list: D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D047390:Casein Kinase II; D016194:Receptors, N-Methyl-D-Aspartate; C121001:NR2B NMDA receptor