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

Zhou, Yu and Takahashi, Eiki and Li, Weidong and Halt, Amy and Wiltgen, Brian and Ehninger, Dan and Li, Guo-Dong and Hell, Johannes W. and Kennedy, Mary B. and Silva, Alcino J. (2007) Interactions between the NR2B receptor and CaMKII modulate synaptic plasticity and spatial learning. Journal of Neuroscience, 27 (50). pp. 13843-13853. ISSN 0270-6474. PMCID PMC6673634. https://resolver.caltech.edu/CaltechAUTHORS:20120424-143645378

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1523/JNEUROSCI.4486-07.2007 DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6673634PubMed CentralArticle
ORCID:
AuthorORCID
Kennedy, Mary B.0000-0003-1369-0525
Additional Information:© 2007 Society for Neuroscience. Received July 30, 2007; revised Oct. 25, 2007; accepted Oct. 25, 2007. This work was supported by National Institutes of Health Grant 98-069-23 (A.J.S.). We thank Robert A. M. Brown and Anna Matynia for critical discussions and helpful comments, and Edoardo Dado Marcora and Tinh Luong for expert technical assistance.
Funders:
Funding AgencyGrant Number
NIH98-069-23
Subject Keywords:CaMKII; NMDA receptor; synapse; plasticity; learning; memory
Issue or Number:50
PubMed Central ID:PMC6673634
Record Number:CaltechAUTHORS:20120424-143645378
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20120424-143645378
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:30297
Collection:CaltechAUTHORS
Deposited By: Melanie Stefan
Deposited On:26 Apr 2012 15:44
Last Modified:03 Oct 2019 03:49

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