Evidence map›Paper›PMID 32203420›Full record

ArticleNature cell biology2020

Systems analysis of RhoGEF and RhoGAP regulatory proteins reveals spatially organized RAC1 signalling from integrin adhesions.

Paul M Müller, Juliane Rademacher, Richard D Bagshaw, Celina Wortmann, Carolin Barth, Jakobus van Unen, Keziban M Alp, Girolamo Giudice, Rebecca L Eccles, Louise E Heinrich and 24 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature cell biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 151 papers.

0numbers the graph read from it
0cells of the map it votes in
151citing papers in PubMed
23.5field-weighted citation impact, top 1% 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

151 citing papers in PubMed, 260 citations in OpenAlex.

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  16. Building the bridges: molecular mechanisms of tunneling nanotube formation.Cellular and molecular life sciences : CMLS · 2026
    Review
  17. How Functional Variants Reconfigure the Rac2 Conformational Landscape.bioRxiv : the preprint server for biology · 2026
    Article
  18. Article
  19. Article
  20. Article

91 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

34 authors at 7 institutions in 4 countries.

Paul M Müller *Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.ORCID http://orcid.org/0000-0001-9056-4114
Juliane Rademacher *Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
Richard D Bagshaw *Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.ORCID http://orcid.org/0000-0001-5013-4291
Celina WortmannMax-Delbrück-Center for Molecular Medicine, Berlin, Germany.
Carolin BarthMax-Delbrück-Center for Molecular Medicine, Berlin, Germany.
Jakobus van UnenInstitute of Cell Biology, University of Bern, Bern, Switzerland.
Keziban M AlpMax-Delbrück-Center for Molecular Medicine, Berlin, Germany.
Girolamo GiudiceEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, UK.
Rebecca L EcclesMax-Delbrück-Center for Molecular Medicine, Berlin, Germany.
Louise E HeinrichInstitute of Cancer Research, Chester Beatty Laboratories, London, UK.
Patricia Pascual-VargasInstitute of Cancer Research, Chester Beatty Laboratories, London, UK.
Marta Sanchez-CastroLunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.
Lennart BrandenburgMax-Delbrück-Center for Molecular Medicine, Berlin, Germany.
Geraldine MbamaluLunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.
Monika TucholskaLunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.
Lisa SpattMax-Delbrück-Center for Molecular Medicine, Berlin, Germany.
Maciej T CzajkowskiMax-Delbrück-Center for Molecular Medicine, Berlin, Germany.
Robert-William WelkeMax-Delbrück-Center for Molecular Medicine, Berlin, Germany.
Sunqu ZhangLunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.
Vivian NguyenLunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.
Trendelina RrustemiMax-Delbrück-Center for Molecular Medicine, Berlin, Germany.
Philipp TrnkaMax-Delbrück-Center for Molecular Medicine, Berlin, Germany.
Kiara FreitagMax-Delbrück-Center for Molecular Medicine, Berlin, Germany.ORCID http://orcid.org/0000-0002-5244-3140
Brett LarsenLunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.
Oliver PoppMax-Delbrück-Center for Molecular Medicine, Berlin, Germany.
Philipp MertinsMax-Delbrück-Center for Molecular Medicine, Berlin, Germany.ORCID http://orcid.org/0000-0002-2245-528X
Anne-Claude GingrasLunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.ORCID http://orcid.org/0000-0002-6090-4437
Frederick P RothLunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.ORCID http://orcid.org/0000-0002-6628-649X
Karen ColwillLunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.ORCID http://orcid.org/0000-0002-8979-1659
Chris BakalInstitute of Cancer Research, Chester Beatty Laboratories, London, UK.ORCID http://orcid.org/0000-0002-0413-6744
Olivier PertzInstitute of Cell Biology, University of Bern, Bern, Switzerland.ORCID http://orcid.org/0000-0001-8579-4919
Tony PawsonLunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.
Evangelia PetsalakiLunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada. petsalaki@ebi.ac.uk.ORCID http://orcid.org/0000-0002-8294-2995
Oliver RocksMax-Delbrück-Center for Molecular Medicine, Berlin, Germany. oliver.rocks@mdc-berlin.de.ORCID http://orcid.org/0000-0001-6349-9193
Max Delbrück Center · DELunenfeld-Tanenbaum Research Institute · CAInstitute of Cancer Research · GBEuropean Bioinformatics Institute · GBUniversity of Bern · CHUniversity of Toronto · CACanadian Institute for Advanced Research · CA

Funding

Cancer Research UK 20146
6 · The paper itself

Abstract

Rho GTPases are central regulators of the cytoskeleton and, in humans, are controlled by 145 multidomain guanine nucleotide exchange factors (RhoGEFs) and GTPase-activating proteins (RhoGAPs). How Rho signalling patterns are established in dynamic cell spaces to control cellular morphogenesis is unclear. Through a family-wide characterization of substrate specificities, interactomes and localization, we reveal at the systems level how RhoGEFs and RhoGAPs contextualize and spatiotemporally control Rho signalling. These proteins are widely autoinhibited to allow local regulation, form complexes to jointly coordinate their networks and provide positional information for signalling. RhoGAPs are more promiscuous than RhoGEFs to confine Rho activity gradients. Our resource enabled us to uncover a multi-RhoGEF complex downstream of G-protein-coupled receptors controlling CDC42-RHOA crosstalk. Moreover, we show that integrin adhesions spatially segregate GEFs and GAPs to shape RAC1 activity zones in response to mechanical cues. This mechanism controls the protrusion and contraction dynamics fundamental to cell motility. Our systems analysis of Rho regulators is key to revealing emergent organization principles of Rho signalling.

Indexed as

AnimalsCell AdhesionCell LineCell MovementChlorocebus aethiopsComputational BiologyCOS CellsCytoskeletonDogsFibroblastsGene Expression ProfilingGene Expression RegulationGTPase-Activating ProteinsHEK293 CellsHeLa CellsHumansGTPase-Activating ProteinsIntegrinsrac1 GTP-Binding ProteinRAC1 protein, humanRho Guanine Nucleotide Exchange Factors

Identifiers

PMID32203420
OpenAlexW3012860965

What OpenQuestion holds

Textmetadata
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.