Nuclear localization is required for Dishevelled function in Wnt/β-catenin signaling

Itoh, Keiji; Brott, Barbara K; Bae, Gyu-Un; Ratcliffe, Marianne J; Sokol, Sergei Y

doi:10.1186/jbiol20

Cited by 221Wnt/β-catenin signaling in development and cancerDevelopmental Biology and Gene RegulationSignaling Pathways in Disease

Nuclear localization is required for Dishevelled function in Wnt/β-catenin signaling

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Itoh, Keiji, Brott, Barbara K, Bae, Gyu-Un, Ratcliffe, Marianne J, Sokol, Sergei Y·2005·Journal of Biology

DOI 10.1186/jbiol20PMC PMC551520

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Abstract

Background: Dishevelled (Dsh) is a key component of multiple signaling pathways that are initiated by Wnt secreted ligands and Frizzled receptors during embryonic development. Although Dsh has been detected in a number of cellular compartments, the importance of its subcellular distribution for signaling remains to be determined. Results: We report that Dsh protein accumulates in cell nuclei when Xenopus embryonic explants or mammalian cells are incubated with inhibitors of nuclear export or when a specific nuclear-export signal (NES) in Dsh is disrupted by mutagenesis. Dsh protein with a mutated NES, while predominantly nuclear, remains fully active in its ability to stimulate canonical Wnt signaling. Conversely, point mutations in conserved amino-acid residues that are essential for the nuclear localization of Dsh impair the ability of Dsh to activate downstream targets of Wnt signaling. When these conserved residues of Dsh are replaced with an unrelated SV40 nuclear localization signal, full Dsh activity is restored. Consistent with a signaling function for Dsh in the nucleus, treatment of cultured mammalian cells with medium containing Wnt3a results in nuclear accumulation of endogenous Dsh protein. Conclusions: These findings suggest that nuclear localization of Dsh is required for its function in the canonical Wnt/β-catenin signaling pathway. We discuss the relevance of these findings to existing models of Wnt signal transduction to the nucleus.

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Dsh shuttles between the cytoplasm and nucleus.
“recent studies have showed that Dsh shuttles between the cytoplasm and nucleus”
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Authors: Itoh, K., Brott, B. K., Bae, G.-U., Ratcliffe, M. J., & Sokol, S. Y.
Affiliations: Beth Israel Deaconess Medical Center (US)
Corresponding author: Sokol, Sergei Y
ORCID: Itoh, Keiji
Bae, Gyu-Un
Ratcliffe, Marianne J
Sokol, Sergei Y
Venue: Journal of Biology
Publisher: Springer Science and Business Media LLC
Published: 2005-02-15
Volume: 4
Issue: 1
Pages: 3-3
ISSN: 1475-4924 (ISSN-L)
DOI: 10.1186/jbiol20
PMC: PMC551520
OpenAlex: W2122299286
Cited by: 221
References: 61
Citations by year: 2026: 3 · 2025: 6 · 2024: 7 · 2023: 3 · 2022: 9 · 2021: 17 · 2020: 7 · 2019: 10 · 2018: 3 · 2017: 14 · 2016: 5 · 2015: 8 · 2014: 9 · 2013: 13 · 2012: 12
FWCI: 8.03
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/2.0/ (tdm)
creativecommons.org/licenses/by/2.0/ (vor)
Locations: Journal of Biology (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: National Institutes of Health
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Keywords: Dishevelled, nuclear localization, Wnt/β-catenin signaling, nuclear export signal, nuclear localization signal, nuclear accumulation, Wnt3a, Frizzled receptors
MeSH terms: Dishevelled Proteins, Amino Acid Sequence, Animals, Blastomeres, Cell Nucleus, Cells, Cultured, Cytoplasm, Gene Expression Regulation, Humans, Molecular Sequence Data, Mutation, Oligopeptides, Phosphoproteins, Xenopus, Sequence Alignment, Gene Order, Xenopus Proteins, Adaptor Proteins, Signal Transducing, Green Fluorescent Proteins, Nuclear Export Signals, Wnt Proteins, Frizzled Receptors, beta Catenin, Rats

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Nuclear localization is required for Dishevelled function in Wnt/β-catenin signaling

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