title: Interactions between the NR2B receptor and CaMKII modulate synaptic plasticity and spatial learning.
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.
authors: Department of Neurobiology, Semel Institute, Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095-1761, USA.
authors: Yu
authors: Y
authors: Zhou
authors: Eiki
authors: E
authors: Takahashi
authors: Weidong
authors: W
authors: Li
authors: Amy
authors: A
authors: Halt
authors: Brian
authors: B
authors: Wiltgen
authors: Dan
authors: D
authors: Ehninger
authors: Guo-Dong
authors: GD
authors: Li
authors: Johannes W
authors: JW
authors: Hell
authors: Mary B
authors: MB
authors: Kennedy
authors: Alcino J
authors: AJ
authors: Silva
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D008024:Ligands; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009924:Organ Culture Techniques; D010766:Phosphorylation; D011960:Receptors, Estrogen / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000502:physiology*; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: D008024:Ligands; C121001:NR2B NMDA receptor; D011960:Receptors, Estrogen; D016194:Receptors, N-Methyl-D-Aspartate; D011993:Recombinant Fusion Proteins; D013629:Tamoxifen; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2