Cited by 161Neuroscience and Neuropharmacology ResearchProtein Kinase Regulation and GTPase SignalingMemory and Neural Mechanisms

CaMKII Autophosphorylation Is Necessary for Optimal Integration of Ca 2+ Signals during LTP Induction, but Not Maintenance

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Chang, Jui-Yun, Parra-Bueno, Paula, Laviv, Tal, Szatmari, Erzsebet M., Lee, Seok-Jin R., Yasuda, Ryohei·2017·Neuron

Abstract

CaMKII plays a critical role in decoding calcium (Ca 2+) signals to initiate long-lasting synaptic plasticity. However, the properties of CaMKII that mediate Ca 2+ signals in spines remain elusive. Here, we measured CaMKII activity in spines using fast-framing two-photon fluorescence lifetime imaging. Following each pulse during repetitive Ca 2+ elevations, CaMKII activity increased in a stepwise manner. Thr286 phosphorylation slows the decay of CaMKII and thus lowers the frequency required to induce spine plasticity by several fold. In the absence of Thr286 phosphorylation, increasing the stimulation frequency results in high peak mutant CaMKII T286A activity that is sufficient for inducing plasticity. Our findings demonstrate that Thr286 phosphorylation plays an important role in induction of LTP by integrating Ca 2+ signals, and it greatly promotes, but is dispensable for, the activation of CaMKII and LTP.

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Crossref · 10.1016/j.neuron.2017.04.041

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  • T286 autophosphorylation and CaM trapping produce a frequency dependence for CaMKII activation.

    “In essence, T286 autophosphorylation and CaM trapping would produce a frequency dependence for CaMKII activation.”

    From Synaptic memory and CaMKII (2023) · cites this paper as [94]

    The Results and Discussion (page unavailable) show that Thr286 autophosphorylation slows CaMKII activity decay and lowers the stimulation frequency needed to integrate Ca²⁺ signals. The paper discusses Ca²⁺/CaM binding and dissociation, but the passages do not establish CaM trapping as a cause of the frequency dependence. (LLM, conf=0.85)

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  • T286A CaMKII shows little integrated activation with repetitive glutamate uncaging unless substantially higher frequencies are used.

    “This representation is strikingly similar to actual CaMKII responses in synaptic spines stimulated by repetitive glutamate uncaging and, as in FIGURE 3, shows little integrated activation with T286A CaMKII, unless substantially higher frequencies are used (94).”

    From Synaptic memory and CaMKII (2023) · cites this paper as [94]

  • Chang et al. reported that LTP can be expressed in the absence of T286 phosphorylation.

    “Despite these findings suggesting a critical role of T286, it should be noted that Chang et al. (94) reported that LTP can be expressed in the absence of T286 phosphorylation.”

    From Synaptic memory and CaMKII (2023) · cites this paper as [94]

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Authors
Chang, J.-Y., Parra-Bueno, P., Laviv, T., Szatmari, E. M., Lee, S.-J. R., & Yasuda, R.
Affiliations
  • Duke University (US)
  • Max Planck Florida Institute for Neuroscience (US)
  • Duke Medical Center (US)
Corresponding author
Yasuda, Ryohei
Venue
Neuron
Publisher
Elsevier BV
Published
2017-05
Volume
94
Issue
4
Pages
800-808.e4
ISSN
0896-6273 (ISSN-L)
OpenAlex
W2616355480
Cited by
161
References
44
Citations by year
2026: 3 · 2025: 16 · 2024: 20 · 2023: 22 · 2022: 21 · 2021: 19 · 2020: 24 · 2019: 19 · 2018: 13 · 2017: 3 · 2014: 1
FWCI
7.90
Type
journal article
Language
en
Open access
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
Funders
NIH (R01MH080047, 1DP1NS096787)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords
CaMKII, autophosphorylation, long-term potentiation, calcium signaling, synaptic plasticity, dendritic spines, LTP maintenance, stimulation frequency
MeSH terms
Animals, Calcium, Hippocampus, Microscopy, Fluorescence, Neuronal Plasticity, Phosphorylation, Long-Term Potentiation, Pyramidal Cells, Patch-Clamp Techniques, Calcium Signaling, Mice, Calcium-Calmodulin-Dependent Protein Kinase Type 2, CA1 Region, Hippocampal

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