Vinculin–Arp2/3 interaction inhibits branched actin assembly to control migration and proliferation
Vinculin is a mechanotransducer that reinforces links between cell adhesions and linear arrays of actin filaments upon myosin-mediated contractility. Both adhesions to the substratum and neighboring cells, however, are initiated within membrane protrusions that originate from Arp2/3-nucleated branched actin networks. Vinculin has been reported to interact with the Arp2/3 complex, but the role of this interaction remains poorly understood. Here, we compared the phenotypes of vinculin knock-out (KO) cells with those of knock-in (KI-P878A) cells, where the point mutation P878A that impairs the Arp2/3 interaction is introduced in the two vinculin alleles of MCF10A mammary epithelial cells. The interaction of vinculin with Arp2/3 inhibits actin polymerization at membrane protrusions and decreases migration persistence of single cells. In cell monolayers, vinculin recruits Arp2/3 and the vinculin-Arp2/3 interaction participates in cell-cell junction plasticity. Through this interaction, vinculin controls the decision to enter a new cell cycle as a function of cell density.
Authors
- Christophe Le Clainche (ORCID: https://orcid.org/0000-0001-5659-677X)
- Stéphane Romero (ORCID: https://orcid.org/0000-0002-7358-3871)
- Svetlana N. Rubtsova (ORCID: https://orcid.org/0000-0003-4620-7851)
- Dmitry Guschin (ORCID: https://orcid.org/0000-0002-4184-0001)
- Anna Polesskaya (ORCID: https://orcid.org/0000-0002-7835-2335)
- Artem I. Fokin (ORCID: https://orcid.org/0000-0003-2205-8441)
- Pascal Silberzan (ORCID: https://orcid.org/0000-0002-8554-882X)
- Hong Wang (ORCID: https://orcid.org/0000-0002-3120-1679)
- Alexis Gautreau (ORCID: https://orcid.org/0000-0002-2369-4362)
- John James (ORCID: https://orcid.org/0009-0009-1009-0832)
Institutions
- Centre National de la Recherche Scientifique (FR)
- École Polytechnique (FR)
- Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR)
- Université Paris-Saclay (FR)
- Sorbonne Université (FR)
- Institut de Biologie Intégrative de la Cellule (FR)
- CEA Paris-Saclay (FR)
- Physique des Cellules et Cancers (FR)
- Institut Curie (FR)
Publication Details
- Journal
- Life Science Alliance
- Published
- 2024-11-15
- DOI
- https://doi.org/10.26508/lsa.202402583
- Citations
- 9
- Primary Topic
- Cellular Mechanics and Interactions
- Type
- article
- Field-Weighted Citation Impact
- 2.93
Funders
- Agence Nationale de la Recherche
- Fondation ARC pour la Recherche sur le Cancer
- Institut National Du Cancer
- Engineering and Physical Sciences Research Council