Evidence map›Paper›PMID 40421714›Full record

ArticleeLife2025

Optogenetic control of a GEF of RhoA uncovers a signaling switch from retraction to protrusion.

Jean de Seze, Maud Bongaerts, Benoit Boulevard, Mathieu Coppey

Abstract read
In one paragraph

Article in eLife, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Building the bridges: molecular mechanisms of tunneling nanotube formation.Cellular and molecular life sciences : CMLS · 2026
    Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Local RhoA activation induces septin recruitment.bioRxiv : the preprint server for biology · 2025
    Article
  10. Article
  11. 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

4 authors.

Jean de SezeLaboratoire Physico Chimie Curie, Institut Curie, PSL Research University, Sorbonne Université, Paris, France.ORCID https://orcid.org/0000-0002-6183-4303
Maud BongaertsLaboratoire Physico Chimie Curie, Institut Curie, PSL Research University, Sorbonne Université, Paris, France.ORCID https://orcid.org/0000-0003-1971-3767
Benoit BoulevardLaboratoire Physico Chimie Curie, Institut Curie, PSL Research University, Sorbonne Université, Paris, France.
Mathieu CoppeyLaboratoire Physico Chimie Curie, Institut Curie, PSL Research University, Sorbonne Université, Paris, France.ORCID https://orcid.org/0000-0001-8924-3233

Funding

Agence Nationale de la Recherche ANR-10-IDEX-0001-02 PSLAgence Nationale de la Recherche ANR-10-INBS-04Agence Nationale de la Recherche ANR-10-LABX-0038Agence Nationale de la Recherche ANR-10-NANO0207Agence Nationale de la Recherche ANR-17-CONV-0005Association pour la Recherche contre le Cancer ARC
6 · The paper itself

Abstract

The ability of a single protein to trigger different functions is an assumed key feature of cell signaling, yet there are very few examples demonstrating it. Here, using an optogenetic tool to control membrane localization of RhoA nucleotide exchange factors (GEFs), we present a case where the same protein can trigger both protrusion and retraction when recruited to the plasma membrane, polarizing the cell in two opposite directions. We show that the basal concentration of the GEF prior to activation predicts the resulting phenotype. A low concentration leads to retraction, whereas a high concentration triggers protrusion. This unexpected protruding behavior arises from the simultaneous activation of Cdc42 by the GEF and sequestration of active RhoA by the GEF PH domain at high concentrations. We propose a minimal model that recapitulates the phenotypic switch, and we use its predictions to control the two phenotypes within selected cells by adjusting the frequency of light pulses. Our work exemplifies a unique case of control of antagonist phenotypes by a single protein that switches its function based on its concentration or dynamics of activity. It raises numerous open questions about the link between signaling protein and function, particularly in contexts where proteins are highly overexpressed, as often observed in cancer.

Indexed as

Guanine Nucleotide Exchange FactorsOptogeneticsrhoA GTP-Binding ProteinRho Guanine Nucleotide Exchange FactorsSignal Transductioncdc42 GTP-Binding ProteinCell MembraneHumanscdc42 GTP-Binding ProteinGuanine Nucleotide Exchange FactorsrhoA GTP-Binding ProteinRHOA protein, humanRho Guanine Nucleotide Exchange Factorscell biologycell migrationhumanoptogeneticssignaling

Identifiers

PMID40421714
PMCPMC12113259

What OpenQuestion holds

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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.