Autophagy genes promote apoptotic cell corpse clearance

The Caenorhabditis elegans genome contains three rac-like genes, ced-10, mig-2, and rac-2. We report that ced-10, mig-2 and rac-2 act redundantly in axon pathfinding: inactivating one gene had little effect, but inactivating two or more genes perturbed both axon outgrowth and guidance. mig-2 and ced-10 also have redundant functions in some cell migrations. By contrast, ced-10 is uniquely required for cell-corpse phagocytosis, and mig-2 and rac-2 have only subtle roles in this process. Rac activators are also used differentially. The UNC-73 Trio Rac GTP exchange factor affected all Rac pathways in axon pathfinding and cell migration but did not affect cell-corpse phagocytosis. CED-5 DOCK180, which acts with CED-10 Rac in cell-corpse phagocytosis, acted with MIG-2 but not CED-10 in axon pathfinding. Thus, distinct regulatory proteins modulate Rac activation and function in different developmental processes.

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Autophagy genes function sequentially to promote apoptotic cell corpse degradation in the engulfing cell

Journal of Experimental Medicine ◽

10.1084/jem2094oia5 ◽

2012 ◽

Vol 209 (4) ◽

pp. i5-i5

Author(s):

Wei Li ◽

Wei Zou ◽

Yihong Yang ◽

Yongping Chai ◽

Baohui Chen ◽

...

Keyword(s):

Apoptotic Cell ◽

Cell Corpse

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CED-10-WASP-Arp2/3 signaling axis regulates apoptotic cell corpse engulfment in C. elegans

Developmental Biology ◽

10.1016/j.ydbio.2017.06.005 ◽

2017 ◽

Vol 428 (1) ◽

pp. 215-223 ◽

Cited By ~ 2

Author(s):

Dou Wu ◽

Yongping Chai ◽

Zhiwen Zhu ◽

Wenjing Li ◽

Guangshuo Ou ◽

...

Keyword(s):

Apoptotic Cell ◽

C Elegans ◽

Signaling Axis ◽

Cell Corpse ◽

Corpse Engulfment

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Rapid cell corpse clearance by stabilin-2, a membrane phosphatidylserine receptor

Cell Death and Differentiation ◽

10.1038/sj.cdd.4402242 ◽

2007 ◽

Vol 15 (1) ◽

pp. 192-201 ◽

Cited By ~ 279

Author(s):

S-Y Park ◽

M-Y Jung ◽

H-J Kim ◽

S-J Lee ◽

S-Y Kim ◽

...

Keyword(s):

Phosphatidylserine Receptor ◽

Cell Corpse ◽

Cell Corpse Clearance

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The amino acid transporter SLC-36.1 cooperates with PtdIns3P 5-kinase to control phagocytic lysosome reformation

The Journal of Cell Biology ◽

10.1083/jcb.201901074 ◽

2019 ◽

Vol 218 (8) ◽

pp. 2619-2637 ◽

Cited By ~ 3

Author(s):

Qiwen Gan ◽

Xin Wang ◽

Qian Zhang ◽

Qiuyuan Yin ◽

Youli Jian ◽

...

Keyword(s):

Amino Acid ◽

Caenorhabditis Elegans ◽

Amino Acid Transporter ◽

Apoptotic Cells ◽

Phagosome Maturation ◽

Genetic Pathway ◽

C Elegans ◽

Acid Transporter ◽

Cell Corpse ◽

Cell Corpse Clearance

Phagocytic removal of apoptotic cells involves formation, maturation, and digestion of cell corpse–containing phagosomes. The retrieval of lysosomal components following phagolysosomal digestion of cell corpses remains poorly understood. Here we reveal that the amino acid transporter SLC-36.1 is essential for lysosome reformation during cell corpse clearance in Caenorhabditis elegans embryos. Loss of slc-36.1 leads to formation of phagolysosomal vacuoles arising from cell corpse–containing phagosomes. In the absence of slc-36.1, phagosome maturation is not affected, but the retrieval of lysosomal components is inhibited. Moreover, loss of PPK-3, the C. elegans homologue of the PtdIns3P 5-kinase PIKfyve, similarly causes accumulation of phagolysosomal vacuoles that are defective in phagocytic lysosome reformation. SLC-36.1 and PPK-3 function in the same genetic pathway, and they directly interact with one another. In addition, loss of slc-36.1 and ppk-3 causes strong defects in autophagic lysosome reformation in adult animals. Our findings thus suggest that the PPK-3–SLC-36.1 axis plays a central role in both phagocytic and autophagic lysosome formation.

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The lysosomal cathepsin protease CPL-1 plays a leading role in phagosomal degradation of apoptotic cells in Caenorhabditis elegans

Molecular Biology of the Cell ◽

10.1091/mbc.e14-01-0015 ◽

2014 ◽

Vol 25 (13) ◽

pp. 2071-2083 ◽

Cited By ~ 16

Author(s):

Meng Xu ◽

Yubing Liu ◽

Liyuan Zhao ◽

Qiwen Gan ◽

Xiaochen Wang ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Apoptotic Cell ◽

Cell Types ◽

Apoptotic Cells ◽

C Elegans ◽

Lysosomal Protease ◽

Leading Role ◽

Lysosomal Proteases ◽

Cell Corpse

During programmed cell death, the clearance of apoptotic cells is achieved by their phagocytosis and delivery to lysosomes for destruction in engulfing cells. However, the role of lysosomal proteases in cell corpse destruction is not understood. Here we report the identification of the lysosomal cathepsin CPL-1 as an indispensable protease for apoptotic cell removal in Caenorhabditis elegans. We find that loss of cpl-1 function leads to strong accumulation of germ cell corpses, which results from a failure in degradation rather than engulfment. CPL-1 is expressed in a variety of cell types, including engulfment cells, and its mutation does not affect the maturation of cell corpse–containing phagosomes, including phagosomal recruitment of maturation effectors and phagosome acidification. Of importance, we find that phagosomal recruitment and incorporation of CPL-1 occurs before digestion of cell corpses, which depends on factors required for phagolysosome formation. Using RNA interference, we further examine the role of other candidate lysosomal proteases in cell corpse clearance but find that they do not obviously affect this process. Collectively, these findings establish CPL-1 as the leading lysosomal protease required for elimination of apoptotic cells in C. elegans.

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