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WGEF activates Rho in the Wnt–PCP pathway and controls convergent extension in Xenopus gastrulation
Open accessAbstract
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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“For activation of the Rho branch of signaling, Wnt signaling induces a Dsh-Daam1 complex that leads to the activation of Daam1 and consequently activation of the Rho GTPase via at least one Rho guanine exchange factor identified thus far, WGEF.67,81”
From Wnt signal transduction pathways (2008) · cites this paper as [81]
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Vilaspasa, F. L. (2010) · UCL Discovery (University College London)
Metadata
- Authors
- Tanegashima, K., Zhao, H., & Dawid, I. B.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Dawid, Igor B
- Venue
- The EMBO Journal
- Published
- 2008-02-07
- Volume
- 27
- Issue
- 4
- Pages
- 606-617
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- 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
- 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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