CDH-3/Cadherin, YAP-1/YAP and EGL-44/TEAD promote SYX-2/Syntaxin and EFF-1 fusogen-mediated phagosome closure

AbstractPhysical interactions between cells, such as cell-cell junctions, can profoundly impact cell fate. A vital cell fate for normal development and homeostasis is programmed cell death. Cells fated to die must be efficiently cleared away via phagocytosis, and defects are associated with a variety of diseased states. Whether cell-cell physical associations affect programmed cell elimination has not been well-explored. Here we describe,in vivo,a cell-cell adhesion-driven signaling pathway that ensures compartment-specific cell clearance during development. We previously described the specialized cell death program “Compartmentalized Cell Elimination” (CCE) in theC. elegansembryo. During CCE, the tail-spike cell (TSC), a polarized epithelial cell, undergoes a tripartite, ordered, and organized death sequence, allowing for the study of three distinct death modalities in a single cell setting. Prior to its demise, the TSC serves as a scaffold for the tail tip, formed by the hyp10 epithelial cell which develops along the TSC process. The hyp10 cell in turn also serves as the phagocyte for the dying TSC process. Here we present data suggesting that the physical association between the dying TSC and hyp10 phagocyte via CDH-3/cadherin mediates function of the mechanosensitive transcriptional coactivator YAP-1/YAP and its partner EGL-44/TEAD in the hyp10 phagocyte to promote localization of hyp10 SYX-2/Syntaxin around the dying TSC remnant. This pathway facilitates the phagocytic function of EFF-1/fusogen, which we have previously shown to be required for phagosome sealing during CCE. Our work sheds additional light on a poorly understood step of phagocytosis and implicates adhesive forces and signaling between cells as important in cell uptake.