Apoptotic Cell Clearance in Drosophila melanogaster

Abstract

The swift clearance of apoptotic cells (ACs) (efferocytosis) by phagocytes is a critical event during development of all multicellular organisms. It is achieved through phagocytosis by professional or amateur phagocytes. Failure in this process can lead to the development of inflammatory autoimmune or neurodegenerative diseases. AC clearance has been conserved throughout evolution, although many details in its mechanisms remain to be explored. It has been studied in the context of mammalian macrophages, and in the nematode Caenorhabditis elegans, which lacks "professional" phagocytes such as macrophages, but in which other cell types can engulf apoptotic corpses. In Drosophila melanogaster, ACs are engulfed by macrophages, glial, and epithelial cells. Drosophila macrophages perform similar functions to those of mammalian macrophages. They are professional phagocytes that participate in phagocytosis of ACs and pathogens. Study of AC clearance in Drosophila has identified some key elements, like the receptors Croquemort and Draper, promoting Drosophila as a suitable model to genetically dissect this process. In this review, we survey recent works of AC clearance pathways in Drosophila, and discuss the physiological outcomes and consequences of this process.

Keywords: Drosophila melanogaster; apoptosis; macrophages; phagocytosis; signaling pathways.

Figure 1

Overview of corpse recognition and disposal in Drosophila. Key components positioned according to their roles in corpse recognition, internalization, and processing. Some important questions are also indicated. Three engulfment receptors located at the plasma membrane. CRQ (Croquemort), a membrane two-path protein, expressed mainly in the macrophages and its ligand and downstream have not studied clearly; Draper (Ced-1), a membrane single-path protein, expressed mainly in glia of CNS and hemocytes, with its ligands are shown in this figure, phosphorylated Draper interact with Ced-6 thus elevates Jun N-terminal kinase (JNK) signal and maintain Ca⁺ homeostasis; JNK promotes Drpr enrichment both in glia and follicular epithelia (under Ced-12 activation). Integrins, a heterodimer protein, function in epithelial follicle cells and hemocytes to engulf cell corpses. The solid arrows mean the relationship between two proteins; the dotted arrows mean the molecular mechanism linking two pathways or proteins unknown. The purple circles with “P” in them mean phosphate groups. The orange circles with “AC” in them mean apoptotic cells; the rectangle outlined by blue lines means engulfment cells; different proteins or molecules are represented by colored shapes as shown in this figure.