A dying epithelial cell doesn't receive tender treatment from its neighbors. They collaborate to evict it. Now, Slattum et al. reveal how epithelial layers force unwanted cells to leave in a specific direction.
An apoptotic cell sends a warning to its epithelial neighbors. They respond by weaving an intercellular band of actin and myosin that contracts, popping the cell out of the epithelial layer. By closing a potential gap, ejection maintains the layer's integrity. Banished cells can exit the layer from the upper, or apical, surface. Or they can leave from the basal surface, slipping into the underlying tissue. The benefits of basal ejection aren't clear—it might allow recycling of the cell. Slattum et al. probed another mystery about the process—what determines which way the cell departs.
By labeling epithelial cells with tags that recognize only active myosin, the researchers discovered that the two exit routes require different contraction patterns. As little as 10% of the time, evicted cells leave basally. In those cases, only myosin in the upper portion of the surrounding cells clenches, pushing the apoptotic cell down. For an apical escape, myosin also contracts in the portions of the neighboring cells that face the sides and bottom of the dying cell. This compression lifts the apoptotic cell.
What enlists the additional myosin fibers required for an apical exit? The team found that when an upward push is needed, microtubules align toward the sides and bottom of the neighboring cells. The filaments direct p115 RhoGEF toward these cellular surfaces. In turn, p115 RhoGEF switches on RhoA that locally activates myosin. An unanswered question is whether cancer cells exploit the eviction mechanism to spread to other sites in the body.