Evidence map›Paper›PMID 27458145›Full record

ArticleMolecular pharmacology2016

WNT Stimulation Dissociates a Frizzled 4 Inactive-State Complex with Gα12/13.

Elisa Arthofer, Belma Hot, Julian Petersen, Katerina Strakova, Stefan Jäger, Manuel Grundmann, Evi Kostenis, J Silvio Gutkind, Gunnar Schulte

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular pharmacology, 2016. 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
2.8field-weighted citation impact, top 9% 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, 51 citations in OpenAlex.

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  15. Receptor selectivity between the G proteins GαFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019
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  16. Article
  17. GFrontiers in aging neuroscience · 2019
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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

9 authors at 5 institutions in 4 countries.

Elisa ArthoferSection of Receptor Biology and Signaling, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (E.A., B.H., J.P., K.S., S.J., G.S.); Section on Molecular Signal Transduction, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (E.A.); Faculty of Science, Institute of Experimental Biology, Masaryk University, Brno, Czech Republic (K.S., G.S.); Molecular, Cellular and Pharmacobiology Section, Institute for Pharmaceutical Biology, University of Bonn, Bonn, Germany (M.G., E.K.); Department of Pharmacology, Moores Cancer Center, University of California, San Diego, La Jolla, California (J.S.G.).
Belma HotSection of Receptor Biology and Signaling, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (E.A., B.H., J.P., K.S., S.J., G.S.); Section on Molecular Signal Transduction, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (E.A.); Faculty of Science, Institute of Experimental Biology, Masaryk University, Brno, Czech Republic (K.S., G.S.); Molecular, Cellular and Pharmacobiology Section, Institute for Pharmaceutical Biology, University of Bonn, Bonn, Germany (M.G., E.K.); Department of Pharmacology, Moores Cancer Center, University of California, San Diego, La Jolla, California (J.S.G.).
Julian PetersenSection of Receptor Biology and Signaling, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (E.A., B.H., J.P., K.S., S.J., G.S.); Section on Molecular Signal Transduction, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (E.A.); Faculty of Science, Institute of Experimental Biology, Masaryk University, Brno, Czech Republic (K.S., G.S.); Molecular, Cellular and Pharmacobiology Section, Institute for Pharmaceutical Biology, University of Bonn, Bonn, Germany (M.G., E.K.); Department of Pharmacology, Moores Cancer Center, University of California, San Diego, La Jolla, California (J.S.G.).
Katerina StrakovaSection of Receptor Biology and Signaling, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (E.A., B.H., J.P., K.S., S.J., G.S.); Section on Molecular Signal Transduction, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (E.A.); Faculty of Science, Institute of Experimental Biology, Masaryk University, Brno, Czech Republic (K.S., G.S.); Molecular, Cellular and Pharmacobiology Section, Institute for Pharmaceutical Biology, University of Bonn, Bonn, Germany (M.G., E.K.); Department of Pharmacology, Moores Cancer Center, University of California, San Diego, La Jolla, California (J.S.G.).
Stefan JägerSection of Receptor Biology and Signaling, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (E.A., B.H., J.P., K.S., S.J., G.S.); Section on Molecular Signal Transduction, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (E.A.); Faculty of Science, Institute of Experimental Biology, Masaryk University, Brno, Czech Republic (K.S., G.S.); Molecular, Cellular and Pharmacobiology Section, Institute for Pharmaceutical Biology, University of Bonn, Bonn, Germany (M.G., E.K.); Department of Pharmacology, Moores Cancer Center, University of California, San Diego, La Jolla, California (J.S.G.).
Manuel GrundmannSection of Receptor Biology and Signaling, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (E.A., B.H., J.P., K.S., S.J., G.S.); Section on Molecular Signal Transduction, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (E.A.); Faculty of Science, Institute of Experimental Biology, Masaryk University, Brno, Czech Republic (K.S., G.S.); Molecular, Cellular and Pharmacobiology Section, Institute for Pharmaceutical Biology, University of Bonn, Bonn, Germany (M.G., E.K.); Department of Pharmacology, Moores Cancer Center, University of California, San Diego, La Jolla, California (J.S.G.).
Evi KostenisSection of Receptor Biology and Signaling, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (E.A., B.H., J.P., K.S., S.J., G.S.); Section on Molecular Signal Transduction, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (E.A.); Faculty of Science, Institute of Experimental Biology, Masaryk University, Brno, Czech Republic (K.S., G.S.); Molecular, Cellular and Pharmacobiology Section, Institute for Pharmaceutical Biology, University of Bonn, Bonn, Germany (M.G., E.K.); Department of Pharmacology, Moores Cancer Center, University of California, San Diego, La Jolla, California (J.S.G.).
J Silvio GutkindSection of Receptor Biology and Signaling, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (E.A., B.H., J.P., K.S., S.J., G.S.); Section on Molecular Signal Transduction, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (E.A.); Faculty of Science, Institute of Experimental Biology, Masaryk University, Brno, Czech Republic (K.S., G.S.); Molecular, Cellular and Pharmacobiology Section, Institute for Pharmaceutical Biology, University of Bonn, Bonn, Germany (M.G., E.K.); Department of Pharmacology, Moores Cancer Center, University of California, San Diego, La Jolla, California (J.S.G.).
Gunnar SchulteSection of Receptor Biology and Signaling, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (E.A., B.H., J.P., K.S., S.J., G.S.); Section on Molecular Signal Transduction, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (E.A.); Faculty of Science, Institute of Experimental Biology, Masaryk University, Brno, Czech Republic (K.S., G.S.); Molecular, Cellular and Pharmacobiology Section, Institute for Pharmaceutical Biology, University of Bonn, Bonn, Germany (M.G., E.K.); Department of Pharmacology, Moores Cancer Center, University of California, San Diego, La Jolla, California (J.S.G.) gunnar.schulte@ki.se.
Eunice Kennedy Shriver National Institute of Child Health and Human Development · USMasaryk University · CZNational Institutes of Health · USUniversity of California, San Diego · USUniversity of Bonn · DE

Funding

ROLE OF G PROTEINS IN GROWTH CONTROL AND CARCINOGENESISZ01DE000551 · NIDCR · NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH · PI GUTKIND, J · 1992 to 2008
$3.4M
Intramural NIH HHS Z01 DE000551
6 · The paper itself

Abstract

Frizzleds (FZDs) are unconventional G protein-coupled receptors that belong to the class Frizzled. They are bound and activated by the Wingless/Int-1 lipoglycoprotein (WNT) family of secreted lipoglycoproteins. To date, mechanisms of signal initiation and FZD-G protein coupling remain poorly understood. Previously, we showed that FZD6 assembles with Gαi1/Gαq (but not with Gαs, Gαo and Ga12/13), and that these inactive-state complexes are dissociated by WNTs and regulated by the phosphoprotein Dishevelled (DVL). Here, we investigated the inactive-state assembly of heterotrimeric G proteins with FZD4, a receptor important in retinal vascular development and frequently mutated in Norrie disease or familial exudative vitreoretinopathy. Live-cell imaging experiments using fluorescence recovery after photobleaching show that human FZD4 assembles-in a DVL-independent manner-with Gα12/13 but not representatives of other heterotrimeric G protein subfamilies, such as Gαi1, Gαo, Gαs, and Gαq The FZD4-G protein complex dissociates upon stimulation with WNT-3A, WNT-5A, WNT-7A, and WNT-10B. In addition, WNT-induced dynamic mass redistribution changes in untransfected and, even more so, in FZD4 green fluorescent protein-transfected cells depend on Gα12/13 Furthermore, expression of FZD4 and Gα12 or Gα13 in human embryonic kidney 293 cells induces WNT-dependent membrane recruitment of p115-RHOGEF (RHO guanine nucleotide exchange factor, molecular weight 115 kDa), a direct target of Gα12/13 signaling, underlining the functionality of an FZD4-Gα12/13-RHO signaling axis. In summary, Gα12/13-mediated WNT/FZD4 signaling through p115-RHOGEF offers an intriguing and previously unappreciated mechanistic link of FZD4 signaling to cytoskeletal rearrangements and RHO signaling with implications for the regulation of angiogenesis during embryonic and tumor development.

Indexed as

Dishevelled ProteinsFluorescence Recovery After PhotobleachingFluorescence Resonance Energy TransferFrizzled ReceptorsGreen Fluorescent ProteinsGTP-Binding Protein alpha Subunits, G12-G13HEK293 CellsHumansProtein BindingProtein DomainsRho Guanine Nucleotide Exchange FactorsSignal TransductionWnt ProteinsDishevelled ProteinsFrizzled ReceptorsFZD4 protein, humanGreen Fluorescent ProteinsGTP-Binding Protein alpha Subunits, G12-G13Rho Guanine Nucleotide Exchange FactorsWnt Proteins

Identifiers

PMID27458145
PMCPMC5034691
OpenAlexW2499076660

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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.