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C. elegans as a Model System for Studying the Degradation of Engulfed Apoptotic Cells Export

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"In animals, cells undergoing apoptosis are rapidly internalized by other cells via phagocytosis (engulfment) and degraded inside phagocytes. The removal of these dying cells provides a safe means for eliminating unwanted and dangerous cells from animal bodies and actively modulates immune responses. The nematode Caenorhabditis elegans has been established as a model organism for delineating pathways that control the evolutionarily conserved cell-corpse engulfment process. Eight genes, ced-1, -2, -5, -6, -7, -10, and -12, and dyn-1, have been identified to act in two parallel and partially redundant pathways to promote cell-corpse engulfment. On the other hand, little is known about how cell corpses are degraded inside engulfing cells. To understand the mechanisms of cell-corpse degradation, we have developed multiple cellular markers and established a highly sensitive and non-invasive time-lapse imaging protocol, which allow us to monitor the processes of cell-corpse engulfment and degradation in real time within developing embryos. Using this new assay system, we have observed that an engulfed cell corpse is degraded inside a vacuolar structure referred to as a phagosome, and that a number of signaling molecules and intracellular organelles are recruited to the cytoplasmic surface of the phagosome.We have found that dyn-1, which encodes the conserved large GTPase dynamin, plays pivotal roles in both the engulfment and degradation of cell corpses in C. elegans embryos and adult gonads. DYN-1 acts to maintain a source of intracellular vesicles in engulfing cells. In addition, it is essential for the recruitment and fusion of endosomes to extending pseudopods and that of endosomes and lysosomes to maturing phagosomes. These functions of DYN-1 provide necessary membrane materials for the expansion of engulfing cell surface during engulfment and essential substances for the digestion of phagosomal contents during phagosome maturation. Using both forward and reverse genetic approaches, we have identified additional molecules whose functions are essential for the efficient degradation of cell corpses. Epistasis analyses enable us to delineate a signaling pathway led by DYN-1 that regulates the degradation of cell corpses."


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