The role of draper in phagocytic competency, corpse processing, and homeostasis
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The clearance of apoptotic cells is an important process in animal development and homeostasis. Failure to dispose of dead cells leads to developmental defects as well as disease. The removal of dead cells within an organism is accomplished by the process of phagocytosis. Phagocytosis of apoptotic cells is the internalization of a dead cell by another cell. Once internalized, the apoptotic cell is subject to various processing events culminating in the complete degradation of the dead cell. Phagocytosis is carried out by specialized cells, known as professional phagocytes. However, phagocytosis can also be carried out by cells that are specialized for functions other than phagocytosis. These cells are known as nonprofessional phagocytes. Although the process of phagocytosis has been extensively studied, the mechanisms are poorly understood. To better understand phagocytosis, this dissertation has focused on the Drosophila receptor Draper (Drpr). Drpr is a highly conserved transmembrane protein that has been shown to be crucial for proper phagocytosis. In this dissertation, I report novel roles for Drpr function. Specifically I show that in the ovary of Drosophila melanogaster, the germline cells can be induced to die by starvation and their remnants are engulfed by surrounding epithelial follicle cells. During this process, the dying germline activates Drpr in the follicle cells. Drpr then activates c-Jun N-terminal kinase (JNK) leading to upregulation of Drpr as well as other engulfment genes. These results suggest that these nonprofessional phagocytes need to acquire a phagocytic phenotype to become phagocytic. We also report that the absence of Drpr in glia leads to an accumulation of apoptotic neurons in the Drosophila brain. These dead cells persist throughout the lifespan of the organism and are associated with age-dependent neurodegeneration. Our data indicate that corpses persist because of defective phagosome maturation. Target of rapamycin complex 1(TORC1) activation in glia is sufficient to rescue corpse accumulation and neurodegeneration. These results suggest that Drpr is important for phagocytic competency, corpse processing, and homeostasis.