Vinculin–Arp2/3 interaction inhibits branched actin assembly to control migration and proliferation
Year: 2024
Type: article
Abstract: 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.
Source: Life Science Alliance
Institutions: Centre National de la Recherche Scientifique, École Polytechnique, Laboratoire de Biologie Structurale de la Cellule, Sorbonne Université, Physique des Cellules et Cancers, Institut Curie, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Université Paris-Saclay, Institut de Biologie Intégrative de la Cellule
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,500
Awards: G2237698137, G2251014725, Nanoscale organization and dynamics of the molecular machinery that drives cell migration, Bio-inspired active sheets: control of membrane shape dynamics by force-generating biopolymer networks, G461943475, Enlightening cell migration through the development and applications of photoresponsive molecules to remodel actin networks, Role of CD44-mediated iron uptake in the invasive switch of breast cancer through signaling by ARF6, RAB35 and RAC1 GTPases, Mechanotransduction of cell collective behaviors through the actin cytoskeleton, G7627205722
OpenAlex ID: W4404412742