ArticleEMBO reports2023
Frizzled receptors facilitate Tiki inhibition of Wnt signaling at the cell surface.
Article in EMBO reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
6 citing papers in PubMed, 11 citations in OpenAlex.
- Conformational cycling of the Wntless transporter drives trafficking and secretion of Wnt morphogens.Nature communications · 2026Article
- Tiki2 restrains Wnt5a/Ror signaling to limit inflammation in acute kidney injury.Communications biology · 2026Article
- Secreted frizzled-related proteins in angiogenesis: molecular mechanisms and clinical implications.Angiogenesis · 2025Review
- Wnt induces FZD5/8 endocytosis and degradation and the involvement of RSPO-ZNRF3/RNF43 and DVL.eLife · 2025Article
- Mechanistic insights into Wnt-β-catenin pathway activation and signal transduction.Nature reviews. Molecular cell biology · 2025Review
- Frizzled receptors facilitate Tiki inhibition of Wnt signaling at the cell surface.EMBO reports · 2023Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
The membrane-tethered protease Tiki antagonizes Wnt3a signaling by cleaving and inactivating Wnt3a in Wnt-producing cells. Tiki also functions in Wnt-receiving cells to antagonize Wnt signaling by an unknown mechanism. Here, we demonstrate that Tiki inhibition of Wnt signaling at the cell surface requires Frizzled (FZD) receptors. Tiki associates with the Wnt-FZD complex and cleaves the N-terminus of Wnt3a or Wnt5a, preventing the Wnt-FZD complex from recruiting and activating the coreceptor LRP6 or ROR1/2 without affecting Wnt-FZD complex stability. Intriguingly, we demonstrate that the N-terminus of Wnt3a is required for Wnt3a binding to LRP6 and activating β-catenin signaling, while the N-terminus of Wnt5a is dispensable for recruiting and phosphorylating ROR1/2. Both Tiki enzymatic activity and its association with the Wnt-FZD complex contribute to its inhibitory function on Wnt5a. Our study uncovers the mechanism by which Tiki antagonizes Wnt signaling at the cell surface and reveals a negative role of FZDs in Wnt signaling by acting as Tiki cofactors. Our findings also reveal an unexpected role of the Wnt3a N-terminus in the engagement of the coreceptor LRP6.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.