Adhesion-mediated heterogeneous actin organization governs apoptotic cell extrusion

Anh Phuong Le, Jean-François Rupprecht (), René-Marc Mège, Yusuke Toyama, Chwee Teck Lim () and Benoît Ladoux ()
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Anh Phuong Le: National University of Singapore
Jean-François Rupprecht: Aix-Marseille Université, Université de Toulon, CNRS, CPT, Turing Centre for Living Systems
René-Marc Mège: Université de Paris, CNRS, Institut Jacques Monod (IJM)
Yusuke Toyama: National University of Singapore
Chwee Teck Lim: National University of Singapore
Benoît Ladoux: Université de Paris, CNRS, Institut Jacques Monod (IJM)

Nature Communications, 2021, vol. 12, issue 1, 1-18

Abstract: Abstract Apoptotic extrusion is crucial in maintaining epithelial homeostasis. Current literature supports that epithelia respond to extrusion by forming a supracellular actomyosin purse-string in the neighbors. However, whether other actin structures could contribute to extrusion and how forces generated by these structures can be integrated are unknown. Here, we found that during extrusion, a heterogeneous actin network composed of lamellipodia protrusions and discontinuous actomyosin cables, was reorganized in the neighboring cells. The early presence of basal lamellipodia protrusion participated in both basal sealing of the extrusion site and orienting the actomyosin purse-string. The co-existence of these two mechanisms is determined by the interplay between the cell-cell and cell-substrate adhesions. A theoretical model integrates these cellular mechanosensitive components to explain why a dual-mode mechanism, which combines lamellipodia protrusion and purse-string contractility, leads to more efficient extrusion than a single-mode mechanism. In this work, we provide mechanistic insight into extrusion, an essential epithelial homeostasis process.

Date: 2021
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DOI: 10.1038/s41467-020-20563-9

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