Phagoptosis is a frequently occurring nonautonomous cell death pathway in which phagocytes eliminate viable cells. While it is thought that phosphatidylserine (PS) “eat-me” signals on target cells initiate the process, the precise sequence of events is largely unknown. Here, we show that in Drosophila testes, progenitor germ cells are spontaneously removed by neighboring cyst cells through phagoptosis. Using live imaging with multiple markers, we demonstrate that cyst cell-derived early/late endosomes and lysosomes fused around live progenitors to acidify them, before DNA fragmentation and substantial PS exposure on the germ cell surface. Furthermore, the phagocytic receptor Draper is expressed on cyst cell membranes and is necessary for phagoptosis. Significantly, germ cell death is blocked by knockdown of either the endosomal component Rab5 or the lysosomal associated protein Lamp1, within the cyst cells. These data ascribe an active role for phagocytic cyst cells in removal of live germ cell progenitors.
Bibliographical noteFunding Information:
We are grateful to C. Han, M. A. Logan, M. R. Freeman, A. Jenny, D. Bohmann, and B. Lemaitre for the gracious gifts of Drosophila stocks and the Developmental Studies Hybridoma Bank for antibodies that were critical for this study. We thank A. Kolpakov for helping with the live imaging setup. We also thank S. Brown for advice and comments. Israel Science Foundation (207/20).
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