Evidence map›Paper›PMID 42270977›Full record

ArticleNature cell biology2026

Long-range mutual activation establishes Rho and Rac polarity during cell migration.

Henry De Belly, Andreu F Gallén, Evelyn Strickland, Dorothy C Estrada, David Sanchez Godinez, Eric Neiva, Patrick J Zager, Tamas L Nagy, Janis K Burkhardt, Hervé Turlier and 1 more

Abstract read
In one paragraph

Article in Nature cell biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Chemical and Mechanical Regulation of Leukocyte Migration.Cold Spring Harbor perspectives in biology · 2026
    Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Henry De BellyCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA. Henry.DeBelly@UTSouthwestern.edu.ORCID http://orcid.org/0000-0003-2452-4450
Andreu F GallénCenter for Interdisciplinary Research in Biology (CIRB), Collège de France, CNRS, INSERM, Université PSL, Paris, France.
Evelyn StricklandCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA.
Dorothy C EstradaCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA.
David Sanchez GodinezCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA.
Eric NeivaCenter for Interdisciplinary Research in Biology (CIRB), Collège de France, CNRS, INSERM, Université PSL, Paris, France.
Patrick J ZagerCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA.
Tamas L NagyCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-6080-9782
Janis K BurkhardtDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia Research Institute and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-8176-1375
Hervé TurlierCenter for Interdisciplinary Research in Biology (CIRB), Collège de France, CNRS, INSERM, Université PSL, Paris, France. herve.turlier@cnrs.fr.ORCID http://orcid.org/0000-0002-9332-9125
Orion D WeinerCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA. Orion.Weiner@ucsf.edu.ORCID http://orcid.org/0000-0002-1778-6543

Funding

Cellular Decision Making Diversity SupplementR35GM118167 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Orion D Weiner · 2016 to 2026
$10.3M
Membrane tension as a long-range integrator of cell physiologyK99GM154115 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI DE BELLY, HENRY · 2024 to 2025
$239k
American Heart Association (American Heart Association, Inc.) 24PRE1198865EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 Marie Skłodowska-Curie Actions (H2020 Excellent Science - Marie Skłodowska-Curie Actions) 101150259EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020) 101105565EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020) 949267NIGMS NIH HHS R35 GM118167RCUK | Biotechnology and Biological Sciences Research Council (BBSRC) 2019598U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) K99GM154115U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R21AI1739938U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R35GM118167
6 · The paper itself

Abstract

In migrating cells, the GTPase Rac organizes a protrusive front, whereas Rho organizes a contractile back. How these GTPases are positioned at opposite poles remains unclear. We leverage optogenetics, mechanical perturbations, and mathematical modelling to reveal a surprising mechanochemical long-range mutual activation between front and back polarity programmes that complements their well-known local mutual inhibition. Rac-based protrusions elevate membrane tension, stimulating an mTORC2-dependent activation of Rho at the opposite side of the cell. Conversely, Rho-mediated contractility induces cortical-flow-based regulation of phosphoinositide signalling that triggers Rac activation distally. We develop a minimal mechanochemical model to explain how long-range facilitation, together with local inhibition, enables robust Rho and Rac partitioning. Our findings demonstrate how the actin cortex and plasma membrane interact as an integrated mechanochemical system for long-range Rac-Rho patterning. This circuit is required for efficient polarity and migration in primary human T cells and is conserved in epithelial cells, highlighting the generality of this mechanism.

Indexed as

Cell MovementCell Polarityrac GTP-Binding Proteinsrho GTP-Binding ProteinsActinsAnimalsCell MembraneEpithelial CellsHumansMechanistic Target of Rapamycin Complex 2Optogeneticsrac1 GTP-Binding ProteinSignal TransductionActinsMechanistic Target of Rapamycin Complex 2rac1 GTP-Binding Proteinrac GTP-Binding Proteinsrho GTP-Binding Proteins

Identifiers

PMID42270977
PMCPMC13279283

What Socratic 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 Socratic graph.