ArticleNature communications2023
The USP46 deubiquitylase complex increases Wingless/Wnt signaling strength by stabilizing Arrow/LRP6.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 10 citations in OpenAlex.
- A Small-Molecule SLD1121 Activates Wnt/β-Catenin Signaling and Promotes Hair Growth via Targeting the Wnt Coreceptor LRP6.JACS Au · 2026Article
- A Balanced Inversion Polymorphism Exhibits a Dominance Reversal at the Gene Expression Level that Depends on Developmental Context.Molecular biology and evolution · 2025Article
- Long-term benefits of TUDCA supplement in ARSACS zebrafish model.Scientific reports · 2025Article
- Wnt signalosomes: What we know that we do not know.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Wg/Wnt-signaling-induced nuclear translocation of β-catenin is attenuated by a β-catenin peptide through its interference with the IFT-A complex.Cell reports · 2024Article
- The USP46 complex deubiquitylates LRP6 to promote Wnt/β-catenin signaling.Nature communications · 2023Article
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Authors and funding
18 authors at 5 institutions in 1 country.
Funding
Abstract
The control of Wnt receptor abundance is critical for animal development and to prevent tumorigenesis, but the mechanisms that mediate receptor stabilization remain uncertain. We demonstrate that stabilization of the essential Wingless/Wnt receptor Arrow/LRP6 by the evolutionarily conserved Usp46-Uaf1-Wdr20 deubiquitylase complex controls signaling strength in Drosophila. By reducing Arrow ubiquitylation and turnover, the Usp46 complex increases cell surface levels of Arrow and enhances the sensitivity of target cells to stimulation by the Wingless morphogen, thereby increasing the amplitude and spatial range of signaling responses. Usp46 inactivation in Wingless-responding cells destabilizes Arrow, reduces cytoplasmic accumulation of the transcriptional coactivator Armadillo/β-catenin, and attenuates or abolishes Wingless target gene activation, which prevents the concentration-dependent regulation of signaling strength. Consequently, Wingless-dependent developmental patterning and tissue homeostasis are disrupted. These results reveal an evolutionarily conserved mechanism that mediates Wnt/Wingless receptor stabilization and underlies the precise activation of signaling throughout the spatial range of the morphogen gradient.
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