Endothelia extrude apoptotic cells to maintain a constant barrier

Abstract

The vascular system is lined with endothelial cells that, although only existing in a single monolayer, are key in the regulation of vascular barrier function. One of the major challenges these cells face is a routine exposure to environmental stressors that can induce apoptosis. Uncontrolled apoptosis in the endothelial monolayer threatens the ability of the cells to maintain their barrier function, resulting in vascular dysfunction. Therefore, we sought to identify ways in which endothelia maintain a cohesive monolayer during apoptotic events. We found that endothelial cells fated die will undergo a process of apoptotic cellular extrusion, similar to what has been described in the epithelium. We further show that endothelial extrusion uses a conserved S1P-S1PR2-RhoA signaling pathway in order to induce the formation of an actin ring that contracts closed, forcing the dying cell out of the monolayer while simultaneously filling in the gap left behind. Thus, endothelial extrusion successfully removes an apoptotic cell before it compromises the monolayer, preserving the barrier function.