Evidence map›Paper›PMID 24885675›Full record

ArticleBMC biology2014

Molecular dissection of Wnt3a-Frizzled8 interaction reveals essential and modulatory determinants of Wnt signaling activity.

Sumit Kumar, Mihaela Žigman, Trushar R Patel, Benjamin Trageser, Julia Christina Gross, Karolin Rahm, Michael Boutros, Dietmar Gradl, Herbert Steinbeisser, Thomas Holstein and 2 more

Open access · goldAbstract read
In one paragraph

Article in BMC biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.7field-weighted citation impact, top 16% of its field
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

21 citing papers in PubMed, 41 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Synthesis and Frizzled-receptor binding of a WNT5A hairpin-3 peptide.Chemical communications (Cambridge, England) · 2024
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Fatty acid recognition in the Frizzled receptor family.The Journal of biological chemistry · 2019
    Review
  10. Article
  11. Review
  12. The function of endocytosis in Wnt signaling.Cellular and molecular life sciences : CMLS · 2018
    Review
  13. Article
  14. The crystal structure of full-length Sizzled fromThe Journal of biological chemistry · 2017
    Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. 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

12 authors at 4 institutions in 3 countries.

Sumit Kumar
Mihaela Žigman
Trushar R Patel
Benjamin Trageser
Julia Christina Gross
Karolin Rahm
Michael Boutros
Dietmar Gradl
Herbert Steinbeisser
Thomas Holstein
Jörg Stetefeld
Suat ÖzbekCentre for Organismal Studies, Department of Molecular Evolution and Genomics, University of Heidelberg, Im Neuenheimer Feld 329, 69120 Heidelberg, Germany. suat.oezbek@cos.uni-heidelberg.de.
Heidelberg University · DEGerman Cancer Research Center · DEKarlsruhe Institute of Technology · DEUniversity of Manitoba · CA

Funding

Canadian Institutes of Health Research RPA-109759
6 · The paper itself

Abstract

backgroundWnt proteins are a family of secreted signaling molecules that regulate key developmental processes in metazoans. The molecular basis of Wnt binding to Frizzled and LRP5/6 co-receptors has long been unknown due to the lack of structural data on Wnt ligands. Only recently, the crystal structure of the Wnt8-Frizzled8-cysteine-rich-domain (CRD) complex was solved, but the significance of interaction sites that influence Wnt signaling has not been assessed.

resultsHere, we present an extensive structure-function analysis of mouse Wnt3a in vitro and in vivo. We provide evidence for the essential role of serine 209, glycine 210 (site 1) and tryptophan 333 (site 2) in Fz binding. Importantly, we discovered that valine 337 in the site 2 binding loop is critical for signaling without contributing to binding. Mutations in the presumptive second CRD binding site (site 3) partly abolished Wnt binding. Intriguingly, most site 3 mutations increased Wnt signaling, probably by inhibiting Wnt-CRD oligomerization. In accordance, increasing amounts of soluble Frizzled8-CRD protein modulated Wnt3a signaling in a biphasic manner.

conclusionsWe propose a concentration-dependent switch in Wnt-CRD complex formation from an inactive aggregation state to an activated high mobility state as a possible modulatory mechanism in Wnt signaling gradients.

Indexed as

Wnt Signaling PathwayAmino Acid SequenceAnimalsEmbryo, NonmammalianHEK293 CellsHumansMiceModels, BiologicalModels, MolecularMolecular Sequence DataMutant ProteinsPoint MutationProtein BindingProtein Structure, TertiaryReceptors, G-Protein-CoupledSolubilityFzd8 protein, mouseMutant ProteinsReceptors, G-Protein-CoupledWnt3A Protein

Identifiers

PMID24885675
PMCPMC4068752
OpenAlexW2012109938

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.