CaMKII Plays a Nonenzymatic Role in Hippocampal Synaptic Plasticity and Learning by Targeting CaMKII to Synapses
Open accessAbstract
The calcium/calmodulin-dependent kinase type II (CaMKII) holoenzyme of the forebrain predominantly consists of heteromeric complexes of the αCaMKII and βCaMKII isoforms. Yet, in contrast to αCaMKII, the role of βCaMKII in hippocampal synaptic plasticity and learning has not been investigated. Here, we compare two targeted Camk2b mouse mutants to study the role of βCaMKII in hippocampal function. Using a Camk2b(-/-) mutant, in which βCaMKII is absent, we show that both hippocampal-dependent learning and Schaffer collateral-CA1 long-term potentiation (LTP) are highly dependent upon the presence of βCaMKII. We further show that βCaMKII is required for proper targeting of αCaMKII to the synapse, indicating that βCaMKII regulates the distribution of αCaMKII between the synaptic pool and the adjacent dendritic shaft. In contrast, localization of αCaMKII, hippocampal synaptic plasticity and learning were unaffected in the Camk2b(A303R) mutant, in which the calcium/calmodulin-dependent activation of βCaMKII is prevented, while the F-actin binding and bundling property is preserved. This indicates that the calcium/calmodulin-dependent kinase activity of βCaMKII is fully dispensable for hippocampal learning, LTP, and targeting of αCaMKII, but implies a critical role for the F-actin binding and bundling properties of βCaMKII in synaptic function. Together, our data provide compelling support for a model of CaMKII function in which αCaMKII and βCaMKII act in concert, but with distinct functions, to regulate hippocampal synaptic plasticity and learning.
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Deletion of CaMKIIβ impairs LTP, as does deletion of CaMKIIα.
“Interestingly, deletion of CaMKIIβ impairs LTP (121, 172, 175), as does the deletion of CaMKIIα.”
From Synaptic memory and CaMKII (2023) · cites this paper as [175]
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Cites
Shen, K., Teruel, M. N., Subramanian, K., & Meyer, T. (1998) · Neuron · doi:10.1016/s0896-6273(00)80569-3 · Cited by 350 · see citing works
Okamoto, K.-I., Narayanan, R., Lee, S. H., Murata, K., & Hayashi, Y. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0701656104 · Cited by 328 · see citing works
Inhibitory Autophosphorylation of CaMKII Controls PSD Association, Plasticity, and Learning
Elgersma, Y., Fedorov, N. B., Ikonen, S., Choi, E. S., Elgersma, M., Carvalho, O. M., Giese, K. P., & Silva, A. J. (2002) · Neuron · doi:10.1016/s0896-6273(02)01007-3 · Cited by 290 · see citing works
Self-citationvan Woerden, G. M., Harris, K. D., Hojjati, M. R., Gustin, R. M., Qiu, S., de Avila Freire, R., Jiang, Y.-H., Elgersma, Y., & Weeber, E. J. (2007) · Nature Neuroscience · doi:10.1038/nn1845 · Cited by 281 · see citing works
Self-citationAllison, D. W., Chervin, A. S., Gelfand, V. I., & Craig, A. M. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-12-04545.2000 · Cited by 245 · see citing works
Functional Implications of the Subunit Composition of Neuronal CaM Kinase II
Brocke, L., Chiang, L. W., Wagner, P. D., & Schulman, H. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.32.22713 · Cited by 161 · cited 2× · see citing works
“In the hippocampus, CaMKII and CaMKII form a holoenzyme consisting of 12 subunits in a 2:1 ratio (Brocke et al., 1999).”
BackgroundYamagata, Y., Kobayashi, S., Umeda, T., Inoue, A., Sakagami, H., Fukaya, M., Watanabe, M., Hatanaka, N., Totsuka, M., Yagi, T., et al. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.0707-09.2009 · Cited by 146 · see citing works
CaMKIIβ binding to stable F-actin <i>in vivo</i> regulates F-actin filament stability
Lin, Y.-C., & Redmond, L. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0804399105 · Cited by 96 · see citing works
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- Goslin K, Banker G, eds (1991) Culturing nerve cells. Cambridge, MA: MIT.
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Okuno, H., Akashi, K., Ishii, Y., Yagishita-Kyo, N., Suzuki, K., Nonaka, M., Kawashima, T., Fujii, H., Takemoto-Kimura, S., Abe, M., et al. (2012) · Cell · doi:10.1016/j.cell.2012.02.062 · Cited by 310 · see citing works
A spatially resolved brain region- and cell type-specific isoform atlas of the postnatal mouse brain
Joglekar, A., Prjibelski, A., Mahfouz, A., Collier, P., Lin, S., Schlusche, A. K., Marrocco, J., Williams, S. R., Haase, B., Hayes, A., et al. (2021) · Nature Communications · doi:10.1038/s41467-020-20343-5 · Cited by 229 · see citing works
De Novo Mutations in Protein Kinase Genes CAMK2A and CAMK2B Cause Intellectual Disability
Küry, S., van Woerden, G. M., Besnard, T., Proietti Onori, M., Latypova, X., Towne, M. C., Cho, M. T., Prescott, T. E., Ploeg, M. A., Sanders, S., et al. (2017) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2017.10.003 · Cited by 185 · see citing works
Self-citationIncontro, S., Díaz-Alonso, J., Iafrati, J., Vieira, M., Asensio, C. S., Sohal, V. S., Roche, K. W., Bender, K. J., & Nicoll, R. A. (2018) · Nature Communications · doi:10.1038/s41467-018-04439-7 · Cited by 171 · see citing works
Chang, J.-Y., Parra-Bueno, P., Laviv, T., Szatmari, E. M., Lee, S.-J. R., & Yasuda, R. (2017) · Neuron · doi:10.1016/j.neuron.2017.04.041 · Cited by 161 · see citing works
Kim, K., Lakhanpal, G., Lu, H. E., Khan, M., Suzuki, A., Kato Hayashi, M., Narayanan, R., Luyben, T. T., Matsuda, T., Nagai, T., et al. (2015) · Neuron · doi:10.1016/j.neuron.2015.07.023 · Cited by 145 · see citing works
GKAP orchestrates activity-dependent postsynaptic protein remodeling and homeostatic scaling
Shin, S. M., Zhang, N., Hansen, J., Gerges, N. Z., Pak, D. T. S., Sheng, M., & Lee, S. H. (2012) · Nature Neuroscience · doi:10.1038/nn.3259 · Cited by 126 · see citing works
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- Authors
- Borgesius, N. Z., van Woerden, G. M., Buitendijk, G. H. S., Keijzer, N., Jaarsma, D., Hoogenraad, C. C., & Elgersma, Y.
- Affiliations
- Erasmus MC (NL)
- Utrecht University (NL)
- Corresponding author
- Elgersma, Y.
- Venue
- Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2011-07-13
- Volume
- 31
- Issue
- 28
- Pages
- 10141-10148
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6623068
- OpenAlex
- W1967462818
- Cited by
- 124
- References
- 8
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 8 · 2023: 9 · 2022: 10 · 2021: 9 · 2020: 7 · 2019: 4 · 2018: 10 · 2017: 7 · 2016: 7 · 2015: 9 · 2014: 12 · 2013: 10 · 2012: 9
- FWCI
- 4.24
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- 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 › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- CaMKII, CaMKIIα, CAMK2B, hippocampal synaptic plasticity, long-term potentiation, hippocampus-dependent learning, F-actin binding, actin bundling
- MeSH terms
- Animals, Hippocampus, Learning, Synaptic Transmission, Neurons, Synapses, Long-Term Potentiation, Mice, Knockout, Protein Subunits, Mice, Calcium-Calmodulin-Dependent Protein Kinase Type 2
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