The ABC Transporter Eato Promotes Cell Clearance in the Drosophila melanogaster Ovary

The clearance of dead cells is a fundamental process in maintaining tissue homeostasis. Genetic studies in Drosophila melanogaster, Caenorhabditis elegans, and mammals have identified two evolutionarily conserved signaling pathways that act redundantly to regulate this engulfment process: the ced-1/-6/-7 and ced-2/-5/-12 pathways. Of these engulfment genes, only the ced-7/ABCA1 ortholog remains to be identified in D. melanogaster. Homology searches revealed a family of putative ced-7/ABCA1 homologs encoding ABC transporters in D. melanogaster. To determine which of these genes functions similarly to ced-7/ABCA1, we analyzed mutants for engulfment phenotypes in oogenesis, during which nurse cells in each egg chamber undergo programmed cell death and are removed by neighboring phagocytic follicle cells. Our genetic analyses indicate that one of the ABC transporter genes, which we have named Eato, is required for nurse cell clearance in the ovary and acts in the same pathways as drpr, the ced-1 ortholog, and in parallel to Ced-12 in the follicle cells. Additionally, we show that Eato acts in the follicle cells to promote accumulation of the transmembrane receptor Drpr, and promote membrane extensions around the nurse cells for their clearance. Since ABCA class transporters, such as CED-7 and Eato, are known to be involved in lipid trafficking, we propose that Eato acts to transport membrane material to the growing phagocytic cup for cell corpse clearance. Our work presented here identifies Eato as the ced-7 ortholog in D. melanogaster, and demonstrates a role for Eato in Drpr accumulation and phagocytic membrane extensions during nurse cell clearance in the ovary.

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