Cited by 121Wnt/β-catenin signaling in development and cancerDevelopmental Biology and Gene RegulationProtein Kinase Regulation and GTPase Signaling

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WGEF activates Rho in the Wnt–PCP pathway and controls convergent extension in Xenopus gastrulation

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Tanegashima, Kosuke, Zhao, Hui, Dawid, Igor B·2008·The EMBO Journal

DOI 10.1038/emboj.2008.9PMC PMC2262038

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Abstract

The Wnt-PCP (planar cell polarity, PCP) pathway regulates cell polarity and convergent extension movements during axis formation in vertebrates by activation of Rho and Rac, leading to the re-organization of the actin cytoskeleton. Rho and Rac activation require guanine nucleotide-exchange factors (GEFs), but the identity of the GEF involved in Wnt-PCP-mediated convergent extension is unknown. Here we report the identification of the weak-similarity GEF (WGEF) gene by a microarray-based screen for notochord enriched genes, and show that WGEF is involved in Wnt-regulated convergent extension. Overexpression of WGEF activated RhoA and rescued the suppression of convergent extension by dominant-negative Wnt-11, whereas depletion of WGEF led to suppression of convergent extension that could be rescued by RhoA or Rho-associated kinase activation. WGEF protein preferentially localized at the plasma membrane, and Frizzled-7 induced colocalization of Dishevelled and WGEF. WGEF protein can bind to Dishevelled and Daam-1, and deletion of the Dishevelled-binding domain generates a hyperactive from of WGEF. These results indicate that WGEF is a component of the Wnt-PCP pathway that connects Dishevelled to Rho activation.

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Authors: Tanegashima, K., Zhao, H., & Dawid, I. B.
Affiliations: National Institutes of Health (US)
Corresponding author: Dawid, Igor B
ORCID: Tanegashima, Kosuke
Zhao, Hui
Dawid, Igor B
Venue: The EMBO Journal
Publisher: Springer Science and Business Media LLC
Published: 2008-02-07
Volume: 27
Issue: 4
Pages: 606-617
ISSN: 0261-4189 (ISSN-L)
1460-2075
DOI: 10.1038/emboj.2008.9
PMC: PMC2262038
OpenAlex: W2095189716
Cited by: 121
References: 53
Citations by year: 2026: 2 · 2025: 2 · 2024: 5 · 2023: 5 · 2022: 6 · 2021: 11 · 2020: 4 · 2019: 3 · 2018: 6 · 2017: 4 · 2016: 6 · 2015: 3 · 2014: 12 · 2013: 5 · 2012: 10
FWCI: 5.08
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: The EMBO Journal (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
Japan Society for the Promotion of Science
National Institute of Child Health and Human Development
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 › Protein Kinase Regulation and GTPase Signaling
Keywords: guanine nucleotide exchange factor, Wnt/PCP pathway, planar cell polarity, convergent extension, Xenopus gastrulation, RhoA activation, Rho kinase, Dishevelled, Frizzled-7, notochord, actin cytoskeleton, cell polarity
MeSH terms: Dishevelled Proteins, Animals, Cell Line, Humans, Notochord, Phosphoproteins, Xenopus laevis, Cell Polarity, Guanine Nucleotide Exchange Factors, rho GTP-Binding Proteins, Adaptor Proteins, Signal Transducing, Wnt Proteins, Gastrulation

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WGEF activates Rho in the Wnt–PCP pathway and controls convergent extension in Xenopus gastrulation

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