CELL-SUBSTRATE ADHESION AND CELL-CELL JUNCTION COORDINATION IN EPITHELIAL CELL EXTRUSION

Abstract

Apoptotic extrusion is a coupled process when a cell undergoes apoptosis and is actively removed from the epithelia. Here, we find that, during extrusion , a highly inhomogeneous cable exist in the neighboring cells surrounding the dying cell, which is contradictory to the predominant notion that the actomyosin cable is formed in a uniform manner. Concurrently, there were also lamellipodia-based protrusions observed. The existence of these two mechanisms is consistent with the measurement of an anisotropic force field surrounding extrusion site. We hypothesized that the co-existence of these two mechanisms suggest a competition between them due to an interplay between the cell-cell and cell-substrate adhesions. Thus, to better understand the extrusion mechanism, we decided to manipulate the cell-cell and cell-substrate adhesion strengths. By manipulating α-Catenin, a mechano-sensing component of adherens junction, we demonstrate that the reduced cell-cell junction favors the neighboring cells’ decision to form lamellipodial protrusion. Conversely, cells with strengthened cell-cell junction formed more actomyosin cable. Apart from tuning cell-cell junctions, we found that the uniform, multicellular contractile actin cable was also enhanced when cell-substrate adhesion was removed. Our results highlight the importance of the previously-under-appreciated lamellipodia-based protrusion in extrusion that is important to ensure a proper extrusion process.