Programmed cell death and clearance of cell corpses in Caenorhabditis elegans

Abstract

Programmed cell death is critical to the development of diverse animal species from C. elegans to humans. In C. elegans, the cell death program has three genetically distinguishable phases. During the cell suicide phase, the core cell death machinery is activated through a protein interaction cascade. This activates the caspase CED-3, which promotes numerous pro-apoptotic activities including DNA degradation and exposure of the phosphatidylserine "eat me" signal on the cell corpse surface. Specification of the cell death fate involves transcriptional activation of the cell death initiator EGL-1 or the caspase CED-3 by coordinated actions of specific transcription factors in distinct cell types. In the cell corpse clearance stage, recognition of cell corpses by phagocytes triggers several signaling pathways to induce phagocytosis of apoptotic cell corpses. Cell corpse-enclosing phagosomes ultimately fuse with lysosomes for digestion of phagosomal contents. This article summarizes our current knowledge about programmed cell death and clearance of cell corpses in C. elegans.

Developmentally programmed germ cell remodelling by endodermal cell cannibalism

“…In the process of cell corpse engulfment, ced-10 functions with two partially redundant pathways: the ced-1/6/7 (‘Draper/Ced-1’) pathway helps to recognize cell corpses, whereas the ced-2/5/12 (‘CrkII/Dock180/Elmo1’) pathway activates CED-10 18 . Mutations in genes within the ced-1/6/7 pathway ( ced-1, ced-7, nrf-5, ttr-52 ), the ced-2/5/12 pathway ( ced-2, ced-5 ), or both pathways ( ced-1;ced-2 and ced-7;ced-5 ) did not cause PGC lobes to persist in L1 larvae (Supplementary Table 1), indicating that ced-10 functions in PGC lobe scission in a different context than it does in cell corpse engulfment.…”

“…5d). The SH3 domain of LST-4 and SNX9 binds dynamin 18, 20 . Given that both SNX9 and dynamin can deform membranes and function in vesicle scission 21 , we asked whether dynamin (encoded by dyn-1 ) is required for PGC lobe scission.…”

Maintenance of Genome Integrity by Mi2 Homologs CHD-3 and LET-418 in Caenorhabditis elegans

“…egl-1 encodes one of two pro-apoptotic BH3 family members activated in response to insults stemming from DNA damaging agents or from defective chromosome dynamics; as a direct consequence the core apoptotic machinery is engaged (Hofmann et al, 2002;Ye et al, 2014;Wang and Yang, 2016; Figure 1A). We found significantly elevated egl-1 in both let-418(n3536) and chd-3(eh4) mutants as compared to wildtype controls ( Figure 1B-C).…”

Programmed Cell Death DuringCaenorhabditis elegansDevelopment

“…The internalization of an apoptotic cell by a phagocytic cell results in the formation and eventual sealing of a phagosome (membrane-bound compartments containing the phagocytosed target), in which the internalized cell corpse is rapidly degraded (Lu and Zhou 2012;Wang and Yang 2016). This internal degradation may avoid inflammatory and autoimmune responses caused by the release of potentially harmful contents of apoptotic cells.…”

“…This internal degradation may avoid inflammatory and autoimmune responses caused by the release of potentially harmful contents of apoptotic cells. The nascent phagosome-containing apoptotic cells undergo sequential fusion with early (sorting) endosomes, late endosomes, and eventually lysosomes, as well as the gradual acidification of the phagosomal lumen; a process called phagosome maturation (Lu and Zhou 2012;Wang and Yang 2016). The maturation process enables nascent phagosomes to gradually acquire the properties of the donor organelles, including the specific membrane markers, lumen contents, and progressive acidification.…”