Cited by 290Neuroscience and Neuropharmacology ResearchMemory and Neural MechanismsProtein Kinase Regulation and GTPase Signaling

Inhibitory Autophosphorylation of CaMKII Controls PSD Association, Plasticity, and Learning

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Elgersma, Ype, Fedorov, Nikolai B, Ikonen, Sami, Choi, Esther S, Elgersma, Minetta, Carvalho, Ofelia M, Giese, Karl Peter, Silva, Alcino J·2002·Neuron

Abstract

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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Crossref · 10.1016/s0896-6273(02)01007-3

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  • T305A/T306A mutations increase CaMKII levels in PSDs and lower the threshold for LTP.

    “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]

  • The results with genetic deletion of CaMKIIα are variable, some showing roughly a 50% block and some showing a complete block.

    “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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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
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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