During animal development, cells undergoing apoptosis, or programmed cell death, are recognized and internalized by other living cells via phagocytosis, a highly conserved process from nematodes to humans. Phagocytosis removes dying cells before they release harmful cellular contents, actively preventing tissue damage, inflammation, and auto-immune responses. Eight genes (
ced-1, 6, 7,
dyn-1 and
ced-2, 5, 10, 12) are known to act within two partially redundant pathways to promote engulfment of apoptotic cell corpses. Among them, CED-1 has been found to act as a phagocytic receptor that recognizes cell corpses and initiates engulfment. Recently, CED-1 was also found to initiate the degradation of engulfed apoptotic cells. The recognition of cell corpses by CED-1 is dependent on CED-7, a C. elegans homolog of mammalian ABC transporters. Our lab has shown CED-7 is necessary for the efficient exposure of phosphatidylserine (PS) on apoptotic somatic cells. Furthermore, we provide evidence to indicate that PS may act as an "eat-me" signal and a ligand for CED-1. Cells injured by external factors such as trauma or diseases undergo necrosis, a type of caspase-independent cell death, and must also be cleared for the protection of surrounding tissues. In C. elegans, the dominant
mec-4 (dm) mutants provide a model for necrotic-like cell death similar to mammalian necrosis. MEC-4 is the core subunit of a multimeric, mechanically gated Na+ channel complex. The
mec-4 (dm) mutations lead to enhanced ion conductivity and subsequent degeneration of six touch receptor neurons. Chung et al 1 have shown that necrotic cells are engulfed through functions of the apoptotic-cell engulfment machinery. However, the mechanism by which necrotic cells are recognized by engulfing cells still remains unclear. In this study we look at the role of putative "eat me" signals in the engulfment of necrotic cell corpses. Using a reporter for the presence of phosphatidylserine (PS), we found that PS was present on the surface of
mec-4 (dm)-induced necrotic cell corpses. In additon, we have also observed CED-1 recognition and localization around necrotic corpses. As is observed in apoptotic cell death, our work has demonstrated that necrotic cell corpses present "eat me" signals for active recognition. This work thus suggests two distinct cell deaths use a similar mechanism for recognition and subsequent engulfment of cell corpses. Previous studies and work in our lab suggest that CED-7 function is required in both the engulfing and apoptotic cell. We are further addressing the cell-specific role of CED-7 in the engulfment of necrotic cells.1Chung et al. Nat Cell Biol 2, 931-7 (2000).