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J Neurosci. 2007 Dec 12;27(50):13843-53.

Interactions between the NR2B receptor and CaMKII modulate synaptic plasticity and spatial learning.

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1
Department of Neurobiology, Semel Institute, Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095-1761, USA.

Abstract

The NR2B subunit of the NMDA receptor interacts with several prominent proteins in the postsynaptic density, including calcium/calmodulin-dependent protein kinase II (CaMKII). To determine the function of these interactions, we derived transgenic mice expressing a ligand-activated carboxy-terminal NR2B fragment (cNR2B) by fusing this fragment to a tamoxifen (TAM)-dependent mutant of the estrogen receptor ligand-binding domain LBD(G521R). Here, we show that induction by TAM allows the transgenic cNR2B fragment to bind to endogenous CaMKII in neurons. Activation of the LBD(G521R)-cNR2B transgenic protein in mice leads to the disruption of CaMKII/NR2B interactions at synapses. The disruption decreases Thr286 phosphorylation of alphaCaMKII, lowers phosphorylation of a key CaMKII substrate in the postsynaptic membrane (AMPA receptor subunit glutamate receptor 1), and produces deficits in hippocampal long-term potentiation and spatial learning. Together our results demonstrate the importance of interactions between CaMKII and NR2B for CaMKII activity, synaptic plasticity, and learning.

PMID:
18077696
DOI:
10.1523/JNEUROSCI.4486-07.2007
[Indexed for MEDLINE]
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