Dact1 induces Dishevelled oligomerization to facilitate binding partner switch and signalosome formation during convergent extension
Abstract Convergent extension (CE) is a universal morphogenetic engine that promotes polarized tissue extension. In vertebrates, CE is regulated by non-canonical Wnt ligands signaling through “core” proteins of the planar cell polarity (PCP) pathway, including the cytoplasmic protein Dishevelled (Dv...
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Nature Portfolio
2025-03-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-57658-0 |
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| author | Allyson Angermeier Deli Yu Yali Huang Sylvie Marchetto Jean-Paul Borg Chenbei Chang Jianbo Wang |
| author_facet | Allyson Angermeier Deli Yu Yali Huang Sylvie Marchetto Jean-Paul Borg Chenbei Chang Jianbo Wang |
| author_sort | Allyson Angermeier |
| collection | DOAJ |
| description | Abstract Convergent extension (CE) is a universal morphogenetic engine that promotes polarized tissue extension. In vertebrates, CE is regulated by non-canonical Wnt ligands signaling through “core” proteins of the planar cell polarity (PCP) pathway, including the cytoplasmic protein Dishevelled (Dvl), receptor Frizzled (Fz) and tetraspan protein Van gogh-like (Vangl). PCP was discovered in Drosophila to coordinate polarity in the plane of static epithelium, but does not regulate CE in flies. Existing evidence suggests that adopting PCP for CE might be a vertebrate-specific adaptation with incorporation of new regulators. Herein we use Xenopus to investigate Dact1, a chordate-specific protein. Dact1 induces Dvl to form oligomers that dissociate from Vangl, but stay attached with Fz as signalosome-like clusters and co-aggregate with Fz into protein patches upon non-canonical Wnt induction. Functionally, Dact1 antagonizes Vangl, and synergizes with wild-type Dvl but not its oligomerization-defective mutants. We propose that, by promoting Dvl oligomerization, Dact1 couples Dvl binding partner switch with signalosome-like cluster formation to initiate non-canonical Wnt signaling during vertebrate CE. |
| format | Article |
| id | doaj-art-090951c93c4f4fe5a7447c6aaaa4eded |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
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| series | Nature Communications |
| spelling | doaj-art-090951c93c4f4fe5a7447c6aaaa4eded2025-08-20T03:02:21ZengNature PortfolioNature Communications2041-17232025-03-0116111910.1038/s41467-025-57658-0Dact1 induces Dishevelled oligomerization to facilitate binding partner switch and signalosome formation during convergent extensionAllyson Angermeier0Deli Yu1Yali Huang2Sylvie Marchetto3Jean-Paul Borg4Chenbei Chang5Jianbo Wang6Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, 1918 University BlvdDepartment of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, 1918 University BlvdDepartment of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, 1918 University BlvdAix Marseille Univ, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Equipe labellisée Ligue ‘Cell Polarity, Cell Signaling And Cancer’Aix Marseille Univ, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Equipe labellisée Ligue ‘Cell Polarity, Cell Signaling And Cancer’Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, 1918 University BlvdDepartment of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, 1918 University BlvdAbstract Convergent extension (CE) is a universal morphogenetic engine that promotes polarized tissue extension. In vertebrates, CE is regulated by non-canonical Wnt ligands signaling through “core” proteins of the planar cell polarity (PCP) pathway, including the cytoplasmic protein Dishevelled (Dvl), receptor Frizzled (Fz) and tetraspan protein Van gogh-like (Vangl). PCP was discovered in Drosophila to coordinate polarity in the plane of static epithelium, but does not regulate CE in flies. Existing evidence suggests that adopting PCP for CE might be a vertebrate-specific adaptation with incorporation of new regulators. Herein we use Xenopus to investigate Dact1, a chordate-specific protein. Dact1 induces Dvl to form oligomers that dissociate from Vangl, but stay attached with Fz as signalosome-like clusters and co-aggregate with Fz into protein patches upon non-canonical Wnt induction. Functionally, Dact1 antagonizes Vangl, and synergizes with wild-type Dvl but not its oligomerization-defective mutants. We propose that, by promoting Dvl oligomerization, Dact1 couples Dvl binding partner switch with signalosome-like cluster formation to initiate non-canonical Wnt signaling during vertebrate CE.https://doi.org/10.1038/s41467-025-57658-0 |
| spellingShingle | Allyson Angermeier Deli Yu Yali Huang Sylvie Marchetto Jean-Paul Borg Chenbei Chang Jianbo Wang Dact1 induces Dishevelled oligomerization to facilitate binding partner switch and signalosome formation during convergent extension Nature Communications |
| title | Dact1 induces Dishevelled oligomerization to facilitate binding partner switch and signalosome formation during convergent extension |
| title_full | Dact1 induces Dishevelled oligomerization to facilitate binding partner switch and signalosome formation during convergent extension |
| title_fullStr | Dact1 induces Dishevelled oligomerization to facilitate binding partner switch and signalosome formation during convergent extension |
| title_full_unstemmed | Dact1 induces Dishevelled oligomerization to facilitate binding partner switch and signalosome formation during convergent extension |
| title_short | Dact1 induces Dishevelled oligomerization to facilitate binding partner switch and signalosome formation during convergent extension |
| title_sort | dact1 induces dishevelled oligomerization to facilitate binding partner switch and signalosome formation during convergent extension |
| url | https://doi.org/10.1038/s41467-025-57658-0 |
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