ArticleThe Journal of biological chemistry2017
Autoinhibition of Dishevelled protein regulated by its extreme C terminus plays a distinct role in Wnt/β-catenin and Wnt/planar cell polarity (PCP) signaling pathways.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 39 citations in OpenAlex.
- The abnormal C-terminus caused by DVL1 variants impacts Robinow syndrome phenotypes.Human molecular genetics · 2026Article
- Dishevelled PDZ domain targeting peptides modulate non-canonical Wnt5a/Ror signaling.Biochemistry and biophysics reports · 2026Article
- A Unique Trimeric Assembly of Human Dishevelled 1 PDZ Domain in Crystal: Implication of Homo- and Hetero-Oligomerization During Wnt Signaling Process.Molecules (Basel, Switzerland) · 2025Article
- Review
- Carboxy-terminal polyglutamylation regulates signaling and phase separation of the Dishevelled protein.The EMBO journal · 2024Article
- Article
- Canonical and Non-Canonical Wnt Signaling Generates Molecular and Cellular Asymmetries to Establish Embryonic Axes.Journal of developmental biology · 2024Review
- Wnt signaling pathway in spinal cord injury: from mechanisms to potential applications.Frontiers in molecular neuroscience · 2024Review
- Disheveled-1 Interacts with Claudin-5 and Contributes to Norrin-Induced Endothelial Barrier Restoration.Cells · 2023Article
- Mechanistic studies in Drosophila and chicken give new insights into functions of DVL1 in dominant Robinow syndrome.Disease models & mechanisms · 2023Article
- Blocking the Wnt/β‑catenin signaling pathway to treat colorectal cancer: Strategies to improve current therapies (Review).International journal of oncology · 2023Review
- Successful therapeutic intervention in new mouse models of frizzled 2-associated congenital malformations.Development (Cambridge, England) · 2023Article
- Wnt4 and ephrinB2 instruct apical constriction via Dishevelled and non-canonical signaling.Nature communications · 2023Article
- Non-canonical WNT5A-ROR signaling: New perspectives on an ancient developmental pathway.Current topics in developmental biology · 2023Article
- Wnt/planar cell polarity signaling controls morphogenetic movements of gastrulation and neural tube closure.Cellular and molecular life sciences : CMLS · 2022Review
- Superresolution microscopy localizes endogenous Dvl2 to Wnt signaling-responsive biomolecular condensates.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Proteomic analysis identifies the E3 ubiquitin ligase Pdzrn3 as a regulatory target of Wnt5a-Ror signaling.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Decoding Dishevelled-Mediated Wnt Signaling in Vertebrate Early Development.Frontiers in cell and developmental biology · 2020Review
- Robinow syndrome skeletal phenotypes caused by the WNT5AC83S variant are due to dominant interference with chondrogenesis.Human molecular genetics · 2019Article
- Dishevelled-3 conformation dynamics analyzed by FRET-based biosensors reveals a key role of casein kinase 1.Nature communications · 2019Article
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
Dishevelled (Dvl) is a key intracellular signaling molecule that mediates the activation of divergent Wnt pathways. It contains three highly conserved domains known as DIX, PDZ, and DEP, the functions of which have been well characterized in β-catenin-dependent canonical and β-catenin-independent noncanonical Wnt signaling. The C-terminal region is also highly conserved from invertebrates to vertebrates. However, its function in regulating the activation of different Wnt signals remains unclear. We reported previously that Dvl conformational change triggered by the highly conserved PDZ-binding C terminus is important for the pathway specificity. Here we provide further evidence demonstrating that binding of the C terminus to the PDZ domain results in Dvl autoinhibition in the Wnt signaling pathways. Therefore, the forced binding of the C terminus to the PDZ domain reduces the activity of Dvl in noncanonical Wnt signaling, whereas obstruction of this interaction releases Dvl autoinhibition, impairs its functional interaction with LRP6 in canonical Wnt signaling, and increases its specificity in noncanonical Wnt signaling, which is closely correlated with an enhanced Dvl membrane localization. Our findings highlight the importance of the C terminus in keeping Dvl in an appropriate autoinhibited state, accessible for regulation by other partners to switch pathway specificity. Particularly, the C-terminally tagged Dvl fusion proteins that have been widely used to study the function and cellular localization of Dvl may not truly represent the wild-type Dvl because those proteins cannot be autoinhibited.
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