Evidence map›Paper›PMID 31000703›Full record

ArticleNature communications2019

Dishevelled-3 conformation dynamics analyzed by FRET-based biosensors reveals a key role of casein kinase 1.

Jakub Harnoš, Maria Consuelo Alonso Cañizal, Miroslav Jurásek, Jitender Kumar, Cornelia Holler, Alexandra Schambony, Kateřina Hanáková, Ondřej Bernatík, Zbyněk Zdráhal, Kristína Gömöryová and 11 more

Abstract read
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing 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

19 citing papers in PubMed.

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  18. Decoding Dishevelled-Mediated Wnt Signaling in Vertebrate Early Development.Frontiers in cell and developmental biology · 2020
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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

21 authors.

Jakub HarnošDepartment of Experimental Biology, Faculty of Science, Masaryk University, Brno, 62500, Czech Republic.
Maria Consuelo Alonso CañizalDepartment of Pharmacology and Toxicology, University of Würzburg, Würzburg, 97078, Germany.ORCID http://orcid.org/0000-0002-3030-8319
Miroslav JurásekCEITEC-Central European Institute of Technology, Masaryk University, Brno, 62500, Czech Republic.
Jitender KumarCEITEC-Central European Institute of Technology, Masaryk University, Brno, 62500, Czech Republic.ORCID http://orcid.org/0000-0002-2465-2391
Cornelia HollerMax Planck Institute for the Science of Light, Erlangen, 91058, Germany.ORCID http://orcid.org/0000-0002-3108-9437
Alexandra SchambonyMax Planck Institute for the Science of Light, Erlangen, 91058, Germany.ORCID http://orcid.org/0000-0001-8771-5487
Kateřina HanákováCEITEC-Central European Institute of Technology, Masaryk University, Brno, 62500, Czech Republic.
Ondřej BernatíkDepartment of Experimental Biology, Faculty of Science, Masaryk University, Brno, 62500, Czech Republic.
Zbyněk ZdráhalCEITEC-Central European Institute of Technology, Masaryk University, Brno, 62500, Czech Republic.
Kristína GömöryováDepartment of Experimental Biology, Faculty of Science, Masaryk University, Brno, 62500, Czech Republic.ORCID http://orcid.org/0000-0003-4407-3917
Tomáš GybeľDepartment of Experimental Biology, Faculty of Science, Masaryk University, Brno, 62500, Czech Republic.
Tomasz Witold RadaszkiewiczDepartment of Experimental Biology, Faculty of Science, Masaryk University, Brno, 62500, Czech Republic.
Marek KravecDepartment of Experimental Biology, Faculty of Science, Masaryk University, Brno, 62500, Czech Republic.
Lukáš TrantírekCEITEC-Central European Institute of Technology, Masaryk University, Brno, 62500, Czech Republic.ORCID http://orcid.org/0000-0001-5948-4837
Jan RynešCEITEC-Central European Institute of Technology, Masaryk University, Brno, 62500, Czech Republic.
Zankruti DaveDepartment of Experimental Biology, Faculty of Science, Masaryk University, Brno, 62500, Czech Republic.ORCID http://orcid.org/0000-0002-3786-0747
Ana Iris Fernández-LlamazaresPepscan Therapeutics B.V., Lelystad, 8243, The Netherlands.ORCID http://orcid.org/0000-0001-9400-5571
Robert VáchaCEITEC-Central European Institute of Technology, Masaryk University, Brno, 62500, Czech Republic.
Konstantinos TripsianesCEITEC-Central European Institute of Technology, Masaryk University, Brno, 62500, Czech Republic.ORCID http://orcid.org/0000-0003-0948-813X
Carsten HoffmannDepartment of Pharmacology and Toxicology, University of Würzburg, Würzburg, 97078, Germany.ORCID http://orcid.org/0000-0003-0884-9300
Vítězslav BryjaDepartment of Experimental Biology, Faculty of Science, Masaryk University, Brno, 62500, Czech Republic. bryja@sci.muni.cz.ORCID http://orcid.org/0000-0002-9136-5085

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Dishevelled (DVL) is the key component of the Wnt signaling pathway. Currently, DVL conformational dynamics under native conditions is unknown. To overcome this limitation, we develop the Fluorescein Arsenical Hairpin Binder- (FlAsH-) based FRET in vivo approach to study DVL conformation in living cells. Using this single-cell FRET approach, we demonstrate that (i) Wnt ligands induce open DVL conformation, (ii) DVL variants that are predominantly open, show more even subcellular localization and more efficient membrane recruitment by Frizzled (FZD) and (iii) Casein kinase 1 ɛ (CK1ɛ) has a key regulatory function in DVL conformational dynamics. In silico modeling and in vitro biophysical methods explain how CK1ɛ-specific phosphorylation events control DVL conformations via modulation of the PDZ domain and its interaction with DVL C-terminus. In summary, our study describes an experimental tool for DVL conformational sampling in living cells and elucidates the essential regulatory role of CK1ɛ in DVL conformational dynamics.

Indexed as

AnimalsBiosensing TechniquesCasein Kinase 1 epsilonDishevelled ProteinsEnzyme AssaysFluorescence Resonance Energy TransferFrizzled ReceptorsGene Knockout TechniquesHEK293 CellsHumansMicroscopy, FluorescenceMolecular Dynamics SimulationMutagenesis, Site-DirectedOocytesPDZ DomainsPhosphorylationCasein Kinase 1 epsilonDishevelled ProteinsDVL3 protein, humanFrizzled ReceptorsFZD6 protein, human

Identifiers

PMID31000703
PMCPMC6472409

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Registered trials

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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.