Vinculin Antagonizes Branched Actin in Controlling Membrane Protrusion, Cell Migration and Cell Cycle Progression

James, J.; Fokin, A. I.; Guschin, D. Y.; Wang, H.; Polesskaya, A.; Rubtsova, S. N.; Le Clainche, C.; Silberzan, P.; Gautreau, A. M.; Romero, S.

doi:10.1101/2023.10.09.561480

bioRxiv · 10.1101/2023.10.09.561480

Vinculin Antagonizes Branched Actin in Controlling Membrane Protrusion, Cell Migration and Cell Cycle Progression

James, J.·Fokin, A. I.·Guschin, D. Y.·Wang, H.·Polesskaya, A.·Rubtsova, S. N.·Le Clainche, C.·Silberzan, P.·Gautreau, A. M.·Romero, S.

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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) 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.

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James, J., Fokin, A. I., Guschin, D. Y., Wang, H., Polesskaya, A., Rubtsova, S. N., Le Clainche, C., Silberzan, P., Gautreau, A. M., Romero, S.. 2023-10-09. Vinculin Antagonizes Branched Actin in Controlling Membrane Protrusion, Cell Migration and Cell Cycle Progression. https://doi.org/10.1101/2023.10.09.561480

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