CaMKIIβ Association with the Actin Cytoskeleton Is Regulated by Alternative Splicing
Open accessAbstract
The Ca(2+)/calmodulin (CaM)-dependent protein kinase II (CaMKII)beta has morphogenic functions in neurons not shared by the alpha isoform. CaMKIIbeta contains three exons (v1, v3, and v4) not present in the CaMKIIalpha gene, and two of these exons (v1 and v4) are subject to differential alternative splicing. We show here that CaMKIIbeta, but not alpha, mediated bundling of F-actin filaments in vitro. Most importantly, inclusion of exon v1 was required for CaMKIIbeta association with the F-actin cytoskeleton within cells. CaMKIIbetae, which is the dominant variant around birth and lacks exon v1 sequences, failed to associate with F-actin. By contrast, CaMKIIbeta', which instead lacks exon v4, associated with F-actin as full-length CaMKIIbeta. Previous studies with CaMKIIbeta mutants have indicated a role of nonstimulated kinase activity in enhancing dendritic arborization. Here, we show that F-actin-targeted CaMKIIbeta, but not alpha, was able to phosphorylate actin in vitro even by nonstimulated basal activity in absence of Ca(2+)/CaM. In rat pancreatic islets and in skeletal muscle, the actin-associated CaMKIIbeta' and betaM were the predominant variants, respectively. Thus, cytoskeletal targeting may mediate functions of CaMKIIbeta variants also outside the nervous system.
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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 [173]
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“Notably, splice variant expression seemed segregated, with only one cell expressing more than one splice variant (Brocke et al., 1999).”
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- Authors
- O'Leary, H., Lasda, E., & Bayer, K. U.
- Affiliations
- *Department of Pharmacology,
- Biomedical Sciences Program, and
- University of Colorado Health (US)
- Venue
- Molecular Biology of the Cell
- Published
- 2006-11
- Volume
- 17
- Issue
- 11
- Pages
- 4656-4665
- ISSN
- 1059-1524 (ISSN-L)
- 1939-4586
- PMC
- PMC1635389
- OpenAlex
- W2123834332
- Cited by
- 113
- References
- 10
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 6 · 2023: 12 · 2022: 8 · 2021: 3 · 2020: 4 · 2019: 5 · 2018: 7 · 2017: 5 · 2016: 3 · 2015: 8 · 2014: 8 · 2013: 4 · 2012: 9
- FWCI
- 2.04
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Biology of the Cell (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- National Institutes of Health (DK57516)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-070735, P30DK057516, P30 DK 57516, R21DK070735)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- CaMKIIβ, CaMKIIα, alternative splicing, F-actin bundling, actin phosphorylation, dendritic branching, morphogenesis, pancreatic islets, skeletal muscle, CaMKII isoforms
- MeSH terms
- Actins, Animals, Chlorocebus aethiops, Chickens, Isoenzymes, Actin Cytoskeleton, Phosphorylation, Protein Binding, RNA, Messenger, Rats, Sprague-Dawley, Alternative Splicing, Calcium-Calmodulin-Dependent Protein Kinases, Gene Expression Regulation, Developmental, COS Cells, Gene Expression Profiling, Protein Transport, Mutant Proteins, Rats, Calcium-Calmodulin-Dependent Protein Kinase Type 2
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