Casein Kinase 2 Regulates the NR2 Subunit Composition of Synaptic NMDA Receptors

Antonio Sanz-Clemente, Jose A. Matta, John T R Isaac, Katherine W. Roche*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

140 Scopus citations

Abstract

N-methyl-D-aspartate (NMDA) receptors (NMDARs) play a central role in development, synaptic plasticity, and neurological disease. NMDAR subunit composition defines their biophysical properties and downstream signaling. Casein kinase 2 (CK2) phosphorylates the NR2B subunit within its PDZ-binding domain; however, the consequences for NMDAR localization and function are unclear. Here we show that CK2 phosphorylation of NR2B regulates synaptic NR2B and NR2A in response to activity. We find that CK2 phosphorylates NR2B, but not NR2A, to drive NR2B-endocytosis and remove NR2B from synapses resulting in an increase in synaptic NR2A expression. During development there is an activity-dependent switch from NR2B to NR2A at cortical synapses. We observe an increase in CK2 expression and NR2B phosphorylation over this same critical period and show that the acute activity-dependent switch in NR2 subunit composition at developing hippocampal synapses requires CK2 activity. Thus, CK2 plays a central role in determining the NR2 subunit content of synaptic NMDARs.

Original languageEnglish (US)
Pages (from-to)984-996
Number of pages13
JournalNeuron
Volume67
Issue number6
DOIs
StatePublished - Sep 2010

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint

Dive into the research topics of 'Casein Kinase 2 Regulates the NR2 Subunit Composition of Synaptic NMDA Receptors'. Together they form a unique fingerprint.

Cite this