Adhesion-mediated heterogeneous actin organization governs apoptotic cell extrusion

• Published in: Nature communications Vol. 12; no. 1; p. 397
• Main Authors: Le, Anh Phuong, Rupprecht, Jean-François, Mège, René-Marc, Toyama, Yusuke, Lim, Chwee Teck, Ladoux, Benoît
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.01.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/1; 13/106; 13/2; 14; 14/19; 14/35; 14/63; 631/57/343/1361; 631/80/79/2066; 631/80/82/23; Actin; Actomyosin; Actomyosin - metabolism; Adhesion; Animals; Apoptosis; Apoptosis - physiology; Cables; Cell adhesion; Cell adhesion & migration; Cell Adhesion - physiology; Cell density; Contractility; Cytoskeleton; Dogs; Epithelium - physiology; Extrusion; Homeostasis; Humanities and Social Sciences; Lamellipodia; Life Sciences; Madin Darby Canine Kidney Cells; Mechanical stimuli; Models, Biological; Monolayers; multidisciplinary; Pseudopodia; Pseudopodia - physiology; Science; Science (multidisciplinary); Strings; Substrates; Mechanotransduction; Cellular motility; Apoptosis
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-20563-9

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. Cell extrusion regulates monolayer cell density and is critical in maintaining epithelia integrity, which has implications in homeostasis, development, and cancer progression. Here the authors describe how monolayer integrate mechanical signals from tissue mechanics, cell-cell adhesion, cell-substrate adhesion and cytoskeleton coordinate cell extrusion.