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

Abstract

Physical interactions between cells 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 via phagocytosis, with defects associated with a variety of diseases. How cell-cell physical associations affect programmed cell elimination is not fully understood. Here we describe, in vivo, a cell-cell adhesion-driven signaling pathway that ensures compartment-specific cell clearance. We previously described the specialized cell death program "Compartmentalized Cell Elimination" (CCE) in the C. elegans embryo. During CCE, the tail-spike scaffolding cell (TSC), a polarized epithelial cell with a posteriorly-directed process, is eliminated via an ordered death sequence. The TSC scaffolds the tail tip, formed by the hyp10 epithelial cell, which in turn serves as the phagocyte for the dying TSC process. We have previously provided mechanistic insights into the poorly understood step of phagocytosis, phagosome sealing, reporting that the fusogen EFF-1 helps clear the TSC process specifically. We identify here a genetic pathway that promotes the translocation of EFF-1 to sealing sites. We identify an upstream role for cell-cell physical association and signaling via the cadherin CDH-3, followed by new roles for the transcription factors YAP-1/YAP and EGL-44/TEAD in promoting the localization of SYX-2/Syntaxin around the dying TSC remnant. Moreover, we find that SYX-2, known to promote EFF-1's role in wound healing, also promotes EFF-1 translocation to sites of phagosome closure. Our work sheds additional light on phagosome sealing and implicates cell-cell adhesive forces and signaling as important in cell uptake.