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Inhibitory Autophosphorylation of CaMKII Controls PSD Association, Plasticity, and Learning
Open accessAbstract
To investigate the function of the alpha calcium-calmodulin-dependent kinase II (alphaCaMKII) inhibitory autophosphorylation at threonines 305 and/or 306, we generated knockin mice that express alphaCaMKII that cannot undergo inhibitory phosphorylation. In addition, we generated mice that express the inhibited form of alphaCaMKII, which resembles the persistently phosphorylated kinase at these sites. Our data demonstrate that blocking inhibitory phosphorylation increases CaMKII in the postsynaptic density (PSD), lowers the threshold for hippocampal long-term potentiation (LTP), and results in hippocampal-dependent learning that seems more rigid and less fine-tuned. Mimicking inhibitory phosphorylation dramatically decreased the association of CaMKII with the PSD and blocked both LTP and learning. These data demonstrate that inhibitory phosphorylation has a critical role in plasticity and learning.
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“However, T305A/T306A mutations increase CaMKII levels in PSDs and lower the threshold for LTP (87).”
From Synaptic memory and CaMKII (2023) · cites this paper as [87]
In the citing paper
“the results with the genetic deletion of CaMKIIα are more variable, some showing roughly a 50% block (87, 204–206) but some showing a complete block (121, 207, 208).”
From Synaptic memory and CaMKII (2023) · cites this paper as [87]
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Metadata
- Authors
- Elgersma, Y., Fedorov, N. B., Ikonen, S., Choi, E. S., Elgersma, M., Carvalho, O. M., Giese, K. P., & Silva, A. J.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Silva, Alcino J
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2002-10
- Volume
- 36
- Issue
- 3
- Pages
- 493-505
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2035831063
- Cited by
- 290
- References
- 43
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 17 · 2023: 11 · 2022: 14 · 2021: 9 · 2020: 10 · 2019: 7 · 2018: 11 · 2017: 15 · 2016: 8 · 2015: 8 · 2014: 18 · 2013: 12 · 2012: 18
- FWCI
- 5.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- National Institute on Aging (AG 13622)
- 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, postsynaptic density, long-term potentiation, hippocampal plasticity, hippocampus-dependent learning, knock-in mice, synaptic plasticity
- MeSH terms
- Animals, Electric Stimulation, Female, Hippocampus, Learning, Male, Membrane Potentials, Mice, Transgenic, Synaptic Transmission, Organ Culture Techniques, Phosphorylation, Synaptic Membranes, Gene Expression Regulation, Enzymologic, Presynaptic Terminals, Long-Term Potentiation, Calcium-Calmodulin-Dependent Protein Kinases, Excitatory Amino Acid Antagonists, Maze Learning, Long-Term Synaptic Depression, Mice, Calcium-Calmodulin-Dependent Protein Kinase Type 2
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