Evidence map›Paper›PMID 27744318›Full record

ArticleJournal of cell science2016

Essential role of the Dishevelled DEP domain in a Wnt-dependent human-cell-based complementation assay.

Melissa V Gammons, Trevor J Rutherford, Zachary Steinhart, Stephane Angers, Mariann Bienz

Open access · hybridAbstract read
In one paragraph

Article in Journal of cell science, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
5.0field-weighted citation impact, top 4% 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

63 citing papers in PubMed, 85 citations in OpenAlex.

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  10. Review
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  13. Wnt signalosomes: What we know that we do not know.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025
    Review
  14. Review
  15. Article
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3 more citing papers are in PubMed but not listed here.

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

5 authors at 2 institutions in 2 countries.

Melissa V GammonsMRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Avenue, Cambridge CB2 0QH, UK melissag@mrc-lmb.cam.ac.uk mb2@mrc-lmb.cam.ac.uk.
Trevor J RutherfordMRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Avenue, Cambridge CB2 0QH, UK.
Zachary SteinhartLeslie Dan Faculty of Pharmacy, Room 901, University of Toronto, 144 College Street, Toronto, Ontario, Canada M5S 3M2.
Stephane AngersLeslie Dan Faculty of Pharmacy, Room 901, University of Toronto, 144 College Street, Toronto, Ontario, Canada M5S 3M2.
Mariann BienzMRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Avenue, Cambridge CB2 0QH, UK melissag@mrc-lmb.cam.ac.uk mb2@mrc-lmb.cam.ac.uk.ORCID 0000-0002-7170-8706
MRC Laboratory of Molecular Biology · GBUniversity of Toronto · CA

Funding

Cancer Research UK 15291Cancer Research UK C7379/A15291Medical Research Council MC_U105184273Medical Research Council MC_U105192713
6 · The paper itself

Abstract

Dishevelled (DVL) assembles Wnt signalosomes through dynamic head-to-tail polymerisation by means of its DIX domain. It thus transduces Wnt signals to cytoplasmic effectors including β-catenin, to control cell fates during normal development, tissue homeostasis and also in cancer. To date, most functional studies of Dishevelled relied on its Wnt-independent signalling activity resulting from overexpression, which is sufficient to trigger polymerisation, bypassing the requirement for Wnt signals. Here, we generate a human cell line devoid of endogenous Dishevelled (DVL1- DVL3), which lacks Wnt signal transduction to β-catenin. However, Wnt responses can be restored by DVL2 stably re-expressed at near-endogenous levels. Using this assay to test mutant DVL2, we show that its DEP domain is essential, whereas its PDZ domain is dispensable, for signalling to β-catenin. Our results imply two mutually exclusive functions of the DEP domain in Wnt signal transduction - binding to Frizzled to recruit Dishevelled to the receptor complex, and dimerising to cross-link DIX domain polymers for signalosome assembly. Our assay avoids the caveats associated with overexpressing Dishevelled, and provides a powerful tool for rigorous functional tests of this pivotal human signalling protein.

Indexed as

beta CateninBiological AssayDishevelled ProteinsDown-RegulationFrizzled ReceptorsGene Knockout TechniquesHEK293 CellsHumansMutationPDZ DomainsPeptidesProtein MultimerizationStructure-Activity RelationshipWnt3A ProteinWnt Signaling Pathwaybeta CateninDishevelled ProteinsFrizzled ReceptorsPeptidesWnt3A ProteinDEP domainDishevelledFrizzledPDZ domain

Identifiers

PMID27744318
PMCPMC5087658
OpenAlexW2530298940

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.