Spatial Control of Draper Receptor Signaling Initiates Apoptotic Cell Engulfment

The engulfment of apoptotic cells is essential for tissue homeostasis and responding to damage. Engulfment is mediated by receptors that recognize ligands exposed on apoptotic cells, such as phosphatidylserine (PS). Here, we convert Drosophila S2 cells into proficient phagocytes by transfecting the Draper engulfment receptor and replacing apoptotic cells with PS-coated beads. We show that PS-ligated Draper forms microclusters that exclude a bulky transmembrane phosphatase and recruit phosphotyrosine binding proteins, revealing a triggering mechanism similar to the T cell receptor (TCR). Analogous to the TCR, Draper’s extracellular domain and PS can be replaced with FRB and FKBP respectively, resulting in a rapamycin-inducible engulfment system. However, in contrast to the TCR, we show that localized signaling at Draper microclusters results in time-dependent depolymerization of actin filaments. Collectively, our results reveal mechanistic similarities and differences between the receptors involved in apoptotic corpse clearance and mammalian immunity and demonstrate that engulfment can be reprogrammed towards non-native targets. Condensed title Spatial Control of Engulfment Signaling