Interactions between the NR2B Receptor and CaMKII Modulate Synaptic Plasticity and Spatial Learning

@article{citeulike:2140487, 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 LBDG521R. Here, we show that induction by TAM allows the transgenic cNR2B fragment to bind to endogenous CaMKII in neurons. Activation of the LBDG521R-cNR2B transgenic protein in mice leads to the disruption of CaMKII/NR2B interactions at synapses. The disruption decreases Thr286 phosphorylation of {alpha}CaMKII, 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. 10.1523/JNEUROSCI.4486-07.2007}, author = {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. }, citeulike-article-id = {2140487}, doi = {10.1523/JNEUROSCI.4486-07.2007}, journal = {J. Neurosci.}, keywords = {071218, camkii, hippocampus, nr2b\_subunit, synaptic\_plasticity}, month = {December}, number = {50}, pages = {13843--13853}, posted-at = {2007-12-18 11:12:08}, priority = {2}, title = {Interactions between the NR2B Receptor and CaMKII Modulate Synaptic Plasticity and Spatial Learning}, url = {http://dx.doi.org/10.1523/JNEUROSCI.4486-07.2007}, volume = {27}, year = {2007} }

TY - JOUR ID - citeulike:2140487 L3 - citeulike-article-id:2140487 TI - Interactions between the NR2B Receptor and CaMKII Modulate Synaptic Plasticity and Spatial Learning JF - J. Neurosci. VL - 27 IS - 50 SP - 13843 EP - 13853 N2 - 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 LBDG521R. Here, we show that induction by TAM allows the transgenic cNR2B fragment to bind to endogenous CaMKII in neurons. Activation of the LBDG521R-cNR2B transgenic protein in mice leads to the disruption of CaMKII/NR2B interactions at synapses. The disruption decreases Thr286 phosphorylation of {alpha}CaMKII, 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. 10.1523/JNEUROSCI.4486-07.2007 KW - 071218 KW - camkii KW - hippocampus KW - nr2b_subunit KW - synaptic_plasticity AU - Zhou, Yu AU - Takahashi, Eiki AU - Li, Weidong AU - Halt, Amy AU - Wiltgen, Brian AU - Ehninger, Dan AU - Li, Guo-Dong AU - Hell, Johannes AU - Kennedy, Mary AU - Silva, Alcino PY - 2007/12/12/ UR - http://dx.doi.org/10.1523/JNEUROSCI.4486-07.2007 ER -