Spatiotemporal coupling of caveolae mechanosensing and RhoA-GEFs regulates cell polarity and directional migration
Migrating cells dynamically adapt their morphogenetic programs in response to microenvironmental changes, requiring coordinated spatiotemporal integration of mechanical and biochemical signals. The plasma membrane, through membrane tension and actin dynamics modulation, is essential for cell motility. Caveolae, small plasma membrane invaginations, act as mechanosensors to buffer tension changes under mechanical stress. Recent evidence suggests a role for caveolae in cell migration. Here, we demonstrate that breast cancer cells exhibit a front-rear asymmetry in caveolae and caveolin-1 scaffolds, which is regulated by membrane tension and is crucial for persistent migration and cell directionality. RhoA-driven cell contraction relies on the spatiotemporally coordinated assembly of caveolae and recruitment of RhoA-GEFs at the cell rear. These results are supported by a physical model establishing a feedback loop between local membrane tension and contractility, through caveolae formation and disruption. Our findings underscore the importance of caveolae mechanosensing in regulating RhoA activation and guiding cell migration.
Authors
- Vibha Singh (ORCID: https://orcid.org/0000-0002-1280-6920)
- Anne‐Sophie Macé (ORCID: https://orcid.org/0000-0003-3072-3819)
- Amit Singh Vishen (ORCID: https://orcid.org/0000-0001-8938-0852)
- Pierre Sens (ORCID: https://orcid.org/0000-0003-4523-3791)
- Philippe Bun (ORCID: https://orcid.org/0000-0002-7975-1768)
- Cédric M. Blouin (ORCID: https://orcid.org/0000-0003-0800-0948)
- Christophe Lamaze (ORCID: https://orcid.org/0000-0001-5430-2707)
- Victor Breton (ORCID: https://orcid.org/0000-0003-4433-5665)
- Christine Viaris de Lesegno (ORCID: https://orcid.org/0000-0002-2033-1128)
Institutions
- Centre National de la Recherche Scientifique (FR)
- University Health Network (CA)
- Inserm (FR)
- Université Paris Cité (FR)
- Université Paris Sciences et Lettres (FR)
- Princess Margaret Cancer Centre (CA)
- Sorbonne Université (FR)
- Centre National pour la Recherche Scientifique et Technique (CNRST) (MA)
- Sorbonne Paris Cité (FR)
- Max Planck Institute for the Physics of Complex Systems (DE)
- Institut de Psychiatrie et Neurosciences de Paris (FR)
- Dynamique du noyau (FR)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-12-12
- DOI
- https://doi.org/10.1038/s41467-025-67090-z
- Primary Topic
- Caveolin-1 and cellular processes
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Infrastructures en Biologie Santé et Agronomie
- European Commission
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Fondation pour la Recherche Médicale
- Centre National de la Recherche Scientifique
- Institut National Du Cancer