The ABC transporter Eato promotes cell clearance in the Drosophila melanogaster ovary

The clearance of dead cells is a fundamental process in the maintenance of 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 have revealed a family of putative ced-7/ ABCA1 homologs encoding ATP-binding cassette (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 (NCs) in each egg chamber undergo programmed cell death (PCD) and are removed by neighboring phagocytic follicle cells (FCs). Our genetic analyses indicate that one of the ABC transporter genes, which we have named Eato (Engulfment ABC Transporter in the ovary), is required for NC clearance in the ovary and acts in the same pathways as drpr, the ced-1 ortholog, and in parallel to Ced-12 in the FCs. Additionally, we show that Eato acts in the FCs to promote accumulation of the transmembrane receptor Drpr, and promote membrane extensions around the NCs for their clearance. Since ABCA class transporters, such as CED-7 and ABCA1, 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/ABCA1 ortholog in D. melanogaster, and demonstrates a role for Eato in Drpr accumulation and phagocytic membrane extensions during NC clearance in the ovaryWe thank members of our laboratory for helpful comments and assistance, especially Albert Mondragon, Alla Yalonetskaya, Johnny Elguero, and Victoria Jenkins, and Todd Blute for assistance with microscopy. This work was supported by National institutes of Health grants R01 GM-060574 and R01 GM-094452 to K.M. T.M.C. was supported by National Science Foundation-Research Experiences for Undergraduates (BIO-1659605) and C.V.T. was supported by Boston University's Undergraduate Research Opportunities Program. (R01 GM-060574 - National institutes of Health; R01 GM-094452 - National institutes of Health; BIO-1659605 - National Science Foundation-Research Experiences for Undergraduates; Boston University's Undergraduate Research Opportunities Program)https://www.g3journal.org/content/8/3/833.longPublished versionPublished versio