Evidence map›Paper›PMID 40413190›Full record

ArticleNature communications2025

WNT-induced association of Frizzled and LRP6 is not sufficient for the initiation of WNT/β-catenin signaling.

Jan Hendrik Voss, Zsombor Koszegi, Yining Yan, Emily Shorter, Lukas Grätz, Johanna T Lanner, Davide Calebiro, Gunnar Schulte

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Jan Hendrik VossKarolinska Institutet, Department of Physiology & Pharmacology, Sec. Receptor Biology & Signaling, Biomedicum, S-17165, Stockholm, Sweden.ORCID http://orcid.org/0000-0003-0595-4607
Zsombor KoszegiDepartment of Metabolism and Systems Science, College of Medicine and Health, University of Birmingham, Birmingham, B15 2TT, UK.ORCID http://orcid.org/0000-0003-2192-0159
Yining YanKarolinska Institutet, Department of Physiology & Pharmacology, Sec. Receptor Biology & Signaling, Biomedicum, S-17165, Stockholm, Sweden.
Emily ShorterKarolinska Institutet, Department of Physiology & Pharmacology, Sec. Molecular Muscle Physiology & Pathophysiology, Biomedicum, S-17165, Stockholm, Sweden.
Lukas GrätzKarolinska Institutet, Department of Physiology & Pharmacology, Sec. Receptor Biology & Signaling, Biomedicum, S-17165, Stockholm, Sweden.ORCID http://orcid.org/0000-0001-6755-0742
Johanna T LannerKarolinska Institutet, Department of Physiology & Pharmacology, Sec. Molecular Muscle Physiology & Pathophysiology, Biomedicum, S-17165, Stockholm, Sweden.ORCID http://orcid.org/0000-0002-1222-9473
Davide CalebiroDepartment of Metabolism and Systems Science, College of Medicine and Health, University of Birmingham, Birmingham, B15 2TT, UK.ORCID http://orcid.org/0000-0002-3811-1553
Gunnar SchulteKarolinska Institutet, Department of Physiology & Pharmacology, Sec. Receptor Biology & Signaling, Biomedicum, S-17165, Stockholm, Sweden. gunnar.schulte@ki.se.ORCID http://orcid.org/0000-0002-2700-7013

Funding

Cancerfonden (Swedish Cancer Society) 20 1102 PjFCancerfonden (Swedish Cancer Society) 23 2825 PjDeutsche Forschungsgemeinschaft (German Research Foundation) 504098926Deutsche Forschungsgemeinschaft (German Research Foundation) 520506488Innovative Medicines Initiative (IMI) 875510Vetenskapsrådet (Swedish Research Council) 2019-01190Vetenskapsrådet (Swedish Research Council) 2024-02515Wellcome TrustWellcome Trust (Wellcome) 212313/Z/18/Z
6 · The paper itself

Abstract

The Wingless/Int-1 (WNT) signaling network is essential to orchestrate central physiological processes such as embryonic development and tissue homeostasis. In the currently held tenet, WNT/β-catenin signaling is initiated by WNT-induced recruitment of Frizzleds (FZDs) and LRP5/6 followed by the formation of a multiprotein signalosome complex. Here, we use bioluminescence resonance energy transfer (BRET) to show that different WNT paralogs dynamically trigger FZD-LRP6 association. While WNT-induced receptor interaction was independent of C-terminal LRP6 phosphorylation, it was allosterically modulated by binding of the phosphoprotein Dishevelled (DVL) to FZD. WNT-16B emerged as a ligand of particular interest, as it efficiently promoted FZD-LRP6 association but, unlike WNT-3A, did not lead to WNT/β-catenin signaling. Transcriptomic analysis further revealed distinct transcriptional fingerprints of WNT-3A and WNT-16B stimulation in HEK293 cells. Additionally, single-molecule tracking demonstrated that, despite increasing FZD

Indexed as

beta CateninFrizzled ReceptorsLow Density Lipoprotein Receptor-Related Protein-6Wnt ProteinsWnt Signaling PathwayDishevelled ProteinsHEK293 CellsHumansPhosphorylationProtein BindingWnt3A Proteinbeta CateninDishevelled ProteinsFrizzled ReceptorsLow Density Lipoprotein Receptor-Related Protein-6LRP6 protein, humanWnt3A ProteinWnt Proteins

Identifiers

PMID40413190
PMCPMC12103576

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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.