Interactions between the NR2B Receptor and CaMKII Modulate Synaptic Plasticity and Spatial Learning
Open accessAbstract
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 αCaMKII, 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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Mutations in the GluN2B CTD that cannot bind CaMKII, or competing constructs, produce highly variable effects on LTP, ranging from complete block to no block.
“The second approach utilizes mutations in the CTD of GluN2B that cannot bind CaMKII as replacement for the wt (CaMKII L1298A/R1300Q) (120, 121, 230) or either competing with overexpressed full-length constructs (GluN2B R1300S/Q1303D) (231) or competing by expressing just the wt GluN2B CTD (839–1482) (232). The results are highly variable as reviewed in Ref. 233, ranging from complete block of LTP”
From Synaptic memory and CaMKII (2023) · cites this paper as [232]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Interaction with the NMDA receptor locks CaMKII in an active conformation
Bayer, K.-U., De Koninck, P., Leonard, A. S., Hell, J. W., & Schulman, H. (2001) · Nature · doi:10.1038/35081080 · Cited by 732 · see citing works
Self-citationKim, M. J., Dunah, A. W., Wang, Y. T., & Sheng, M. (2005) · Neuron · doi:10.1016/j.neuron.2005.04.031 · Cited by 494 · see citing works
Rodrigues, S. M., Schafe, G. E., & LeDoux, J. E. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-17-06889.2001 · Cited by 350 · see citing works
Pettit, D. L., Perlman, S., & Malinow, R. (1994) · Science · doi:10.1126/science.7997883 · Cited by 329 · see citing works
Integration of biochemical signalling in spines
Kennedy, M. B., Beale, H. C., Carlisle, H. J., & Washburn, L. R. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1685 · Cited by 286 · see citing works
Self-citationOtmakhov, N., Tao-Cheng, J.-H., Carpenter, S., Asrican, B., Dosemeci, A., Reese, T. S., & Lisman, J. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.2350-04.2004 · Cited by 258 · see citing works
N-Methyl-D-aspartate Receptors: Subunit Assembly and Trafficking to the Synapse
Prybylowski, K., & Wenthold, R. J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.r300029200 · Cited by 137 · see citing works
αCaMKII autophosphorylation contributes to rapid learning but is not necessary for memory
Irvine, E. E., Vernon, J., & Giese, K. P. (2005) · Nature Neuroscience · doi:10.1038/nn1431 · Cited by 119 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Mechanisms of CaMKII action in long-term potentiation
Lisman, J., Yasuda, R., & Raghavachari, S. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3192 · Cited by 1,134 · see citing works
Dnmt1 and Dnmt3a maintain DNA methylation and regulate synaptic function in adult forebrain neurons
Feng, J., Zhou, Y., Campbell, S. L., Le, T., Li, E., Sweatt, J. D., Silva, A. J., & Fan, G. (2010) · Nature Neuroscience · doi:10.1038/nn.2514 · Cited by 1,019 · see citing works
Self-citationAMPARs and Synaptic Plasticity: The Last 25 Years
Huganir, R. L., & Nicoll, R. A. (2013) · Neuron · doi:10.1016/j.neuron.2013.10.025 · Cited by 968 · see citing works
Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels
Hansen, K. B., Wollmuth, L. P., Bowie, D., Furukawa, H., Menniti, F. S., Sobolevsky, A. I., Swanson, G. T., Swanger, S. A., Greger, I. H., Nakagawa, T., et al. (2021) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000131 · Cited by 686 · see citing works
Regulation of NMDA receptor subunit expression and its implications for LTD, LTP, and metaplasticity
Yashiro, K., & Philpot, B. D. (2008) · Neuropharmacology · doi:10.1016/j.neuropharm.2008.07.046 · Cited by 649 · see citing works
Computational principles of memory
Chaudhuri, R., & Fiete, I. (2016) · Nature Neuroscience · doi:10.1038/nn.4237 · Cited by 213 · see citing works
The role of metaplasticity mechanisms in regulating memory destabilization and reconsolidation
Finnie, P. S. B., & Nader, K. (2012) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2012.03.008 · Cited by 189 · see citing works
Moncada, D., Ballarini, F., Martinez, M. C., Frey, J. U., & Viola, H. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1104495108 · Cited by 171 · see citing works
Bodhinathan, K., Kumar, A., & Foster, T. C. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.5485-09.2010 · Cited by 153 · see citing works
Regulation of NMDA glutamate receptor functions by the GluN2 subunits
Vieira, M., Yong, X. L. H., Roche, K. W., & Anggono, V. (2020) · Journal of Neurochemistry · doi:10.1111/jnc.14970 · Cited by 151 · see citing works
Nicoll, R. A., & Schulman, H. (2023) · Physiological Reviews · doi:10.1152/physrev.00034.2022 · Cited by 126 · see citing works
“…approach utilizes mutations in the CTD of GluN2B that cannot bind CaMKII as replacement for the wt (CaMKII L1298A/R1300Q) (120, 121, 230) or either competing with overexpressed full-length constructs (GluN2B R1300S/ Q1303D) (231) or competing by expressing just the wt GluN2B CTD (839 – 1482) (232).”
BackgroundPlasticity of dendritic spines: subcompartmentalization of signaling
Colgan, L. A., & Yasuda, R. (2014) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021113-170400 · Cited by 124 · see citing works
DAPK1 Mediates LTD by Making CaMKII/GluN2B Binding LTP Specific
Goodell, D. J., Zaegel, V., Coultrap, S. J., Hell, J. W., & Bayer, K. U. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.05.068 · Cited by 88 · see citing works
Self-citationSynapse rearrangements upon learning: from divergent–sparse connectivity to dedicated sub-circuits
Caroni, P., Chowdhury, A., & Lahr, M. (2014) · Trends in Neurosciences · doi:10.1016/j.tins.2014.08.011 · Cited by 85 · see citing works
Carlisle, H. J., Luong, T. N., Medina-Marino, A., Schenker, L., Khorosheva, E., Indersmitten, T., Gunapala, K. M., Steele, A. D., O'Dell, T. J., Patterson, P. H., et al. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.5877-10.2011 · Cited by 74 · see citing works
Self-citationKlug, J. R., Mathur, B. N., Kash, T. L., Wang, H.-D., Matthews, R. T., Robison, A. J., Anderson, M. E., Deutch, A. Y., Lovinger, D. M., Colbran, R. J., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0045323 · Cited by 49 · see citing works
Priya, A., Johar, K., & Wong-Riley, M. T. T. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2013.07.002 · Cited by 33 · see citing works
Jiang, H., Jiang, W., Zou, J., Wang, B., Yu, M., Pan, Y., Lin, Y., Mao, Y., & Wang, Y. (2015) · Brain Research · doi:10.1016/j.brainres.2015.03.031 · Cited by 27 · see citing works
- Authors
- Zhou, Y., Takahashi, E., Li, W., Halt, A., Wiltgen, B., Ehninger, D., Li, G.-D., Hell, J. W., Kennedy, M. B., & Silva, A. J.
- Affiliations
- University of California, Los Angeles (US)
- University of Iowa (US)
- California Institute of Technology (US)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2007-12-12
- Volume
- 27
- Issue
- 50
- Pages
- 13843-13853
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6673634
- OpenAlex
- W1970690750
- Cited by
- 179
- References
- 8
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 7 · 2022: 6 · 2021: 14 · 2020: 5 · 2019: 6 · 2018: 12 · 2017: 9 · 2016: 13 · 2015: 12 · 2014: 10 · 2013: 13 · 2012: 20
- FWCI
- 3.58
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- Funders
- National Institutes of Health
- U.S. Public Health Service (98-069-23)
- National Institute of General Medical Sciences (T32GM067795, T32GM007337)
- National Institute of Neurological Disorders and Stroke (R01NS017660)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- NR2B subunit, NMDA receptor, CaMKII, synaptic plasticity, spatial learning, long-term potentiation, AMPA receptors, GluR1, postsynaptic density, hippocampus
- MeSH terms
- Animals, Ligands, Mice, Inbred C57BL, Mice, Transgenic, Neuronal Plasticity, Neurons, Organ Culture Techniques, Phosphorylation, Receptors, Estrogen, Recombinant Fusion Proteins, Synapses, Tamoxifen, Receptors, N-Methyl-D-Aspartate, Long-Term Potentiation, Maze Learning, Long-Term Synaptic Depression, Mice, Calcium-Calmodulin-Dependent Protein Kinase Type 2
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
