Cited by 328Neuroscience and Neuropharmacology ResearchProtein Kinase Regulation and GTPase SignalingGenetics and Neurodevelopmental Disorders

The role of CaMKII as an F-actin-bundling protein crucial for maintenance of dendritic spine structure

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Okamoto, Ken-Ichi, Narayanan, Radhakrishnan, Lee, Sang H., Murata, Kazuyoshi, Hayashi, Yasunori·2007·Proceedings of the National Academy of Sciences

Abstract

Ca 2+ -calmodulin-dependent protein kinase II (CaMKII) is a serine/threonine protein kinase critically involved in synaptic plasticity in the brain. It is highly concentrated in the postsynaptic density fraction, exceeding the amount of any other signal transduction molecules. Because kinase signaling can be amplified by catalytic reaction, why CaMKII exists in such a large quantity has been a mystery. Here, we provide biochemical evidence that CaMKII is capable of bundling F-actin through a stoichiometric interaction. Consistent with this evidence, in hippocampal neurons, RNAi-mediated down-regulation of CaMKII leads to a reduction in the volume of dendritic spine head that is mediated by F-actin dynamics. An overexpression of CaMKII slowed down the actin turnover in the spine head. This activity was associated with β subunit of CaMKII in a manner requiring its actin-binding and association domains but not the kinase domain. This finding indicates that CaMKII serves as a central signaling molecule in both functional and structural changes during synaptic plasticity.

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Crossref · 10.1073/pnas.0701656104

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  • Upon activation CaMKIIβ dissociates from F-actin because of competition with Ca2+/CaM for the F-actin binding region, and dissociation is made more persistent by specific autophosphorylation of CaMKIIβ in the F-actin binding region.

    “Upon activation CaMKIIβ dissociates from F-actin because of competition with Ca2+/CaM for the F-actin binding region, and dissociation is made more persistent by specific autophosphorylation of CaMKIIβ in the F-actin binding region (171–174).”

    From Synaptic memory and CaMKII (2023) · cites this paper as [174]

    The Results section, “Activation of CaMKII Leads to a Loss of Bundling Activity” (page not provided), reports that Ca2+/calmodulin activation reverses CaMKIIβ-mediated F-actin bundling and that autophosphorylation contributes to a longer-lasting reversal. It does not establish that Ca2+/calmodulin competes specifically for the F-actin-binding region, or identify specific phosphorylation sites there as the cause of persistent dissociation. (LLM, conf=0.84)

    Experimental — accuracy not yet measured
  • CaMKII is a calcium-activated kinase involved in structural plasticity by remodeling of the postsynaptic density, rearrangement of the actin cytoskeleton and maintenance of spine enlargement.

    “CaMKII is a calcium-activated kinase involved in structural plasticity by remodeling of the postsynaptic density (Yoshimura et al., 2002), rearrangement of the actin cytoskeleton (Okamoto et al., 2007) and maintenance of spine enlargement (Matsuzaki et al., 2004; Lee et al., 2009).”

    From Barriers in the brain: resolving dendritic spine morphology and compartmentalization (2014) · cites this paper as Okamoto et al., 2007

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  1. [37]Dunnett CW. J Am Stat Assoc. 1955;50:1096–1121. [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Am%20Stat%20Assoc&author=CW%20Dunnett&volume=50&publication_year=1955&pages=1096-1121&)]

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Authors
Okamoto, K.-I., Narayanan, R., Lee, S. H., Murata, K., & Hayashi, Y.
Affiliations
  • *RIKEN-MIT Neuroscience Research Center, The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139;
  • Massachusetts Institute of Technology (US)
  • Medical College of Wisconsin (US)
Corresponding author
Hayashi, Yasunori
Venue
Proceedings of the National Academy of Sciences
Published
2007-04-10
Volume
104
Issue
15
Pages
6418-6423
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2170201765
Cited by
328
References
38
Citations by year
2026: 13 · 2025: 14 · 2024: 12 · 2023: 20 · 2022: 10 · 2021: 13 · 2020: 14 · 2019: 18 · 2018: 20 · 2017: 16 · 2016: 14 · 2015: 19 · 2014: 29 · 2013: 17 · 2012: 20
FWCI
8.49
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Ellison Medical Foundation
  • National Institutes of Health
  • RIKEN
  • National Institute on Drug Abuse (R01DA017310)
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 › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
CaMKII, F-actin bundling, synaptic plasticity, postsynaptic density, actin turnover, beta subunit, actin-binding domain, hippocampal neurons
MeSH terms
Actins, Animals, Hippocampus, Microscopy, Electron, Scanning, Models, Biological, Neuronal Plasticity, Synapses, Signal Transduction, Calcium-Calmodulin-Dependent Protein Kinases, RNA Interference, Dendritic Spines, Rats, Calcium-Calmodulin-Dependent Protein Kinase Type 2

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