Cleaning up the mess: cell corpse clearance in Caenorhabditis elegans

2012 ◽  
Vol 24 (6) ◽  
pp. 881-888 ◽  
Author(s):  
Sérgio Morgado Pinto ◽  
Michael Otmar Hengartner
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Corpse ◽  
Cell Corpse Clearance

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

2019 ◽  
Vol 218 (8) ◽  
pp. 2619-2637 ◽  
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.

scholarly journals Autophagy genes promote apoptotic cell corpse clearance

Autophagy ◽  
2012 ◽  
Vol 8 (8) ◽  
pp. 1267-1268 ◽  
Author(s):  
Wei Zou ◽  
Xiaochen Wang ◽  
Ronald Vale ◽  
Guangshuo Ou
Keyword(s):  
Apoptotic Cell ◽  
Cell Corpse ◽  
Cell Corpse Clearance

scholarly journals NUC-1, a Caenorhabditis elegans DNase II homolog, functions in an intermediate step of DNA degradation during apoptosis

2000 ◽  
Vol 14 (5) ◽  
pp. 536-548 ◽  
Author(s):  
Yi-Chun Wu ◽  
Gillian M. Stanfield ◽  
H. Robert Horvitz
Keyword(s):  
Caenorhabditis Elegans ◽  
Intermediate Stage ◽  
Dna Degradation ◽  
Intermediate Step ◽  
Apoptotic Cells ◽  
Chromosomal Dna ◽  
Dnase Ii ◽  
A Cell ◽  
Cell Corpse ◽  
Transient Intermediate

One hallmark of apoptosis is the degradation of chromosomal DNA. We cloned the Caenorhabditis elegans gene nuc-1, which is involved in the degradation of the DNA of apoptotic cells, and found that nuc-1 encodes a homolog of mammalian DNase II. We used the TUNEL technique to assay DNA degradation in nuc-1 and other mutants defective in programmed cell death and discovered that TUNEL labels apoptotic cells only during a transient intermediate stage. Mutations in nuc-1 allowed the generation of TUNEL-reactive DNA but blocked the conversion of TUNEL-reactive DNA to a subsequent TUNEL-unreactive state. Completion of DNA degradation did not occur in the absence of cell-corpse engulfment. Our data suggest that the process of degradation of the DNA of a cell corpse occurs in at least three distinct steps and requires activities provided by both the dying and the engulfing cell.

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

2007 ◽  
Vol 15 (1) ◽  
pp. 192-201 ◽  
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

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

2014 ◽  
Vol 25 (13) ◽  
pp. 2071-2083 ◽  
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.

scholarly journals Residual body removal during spermatogenesis in C. elegans requires genes that mediate cell corpse clearance

Development ◽  
2012 ◽  
Vol 139 (24) ◽  
pp. 4613-4622 ◽  
Author(s):  
J. Huang ◽  
H. Wang ◽  
Y. Chen ◽  
X. Wang ◽  
H. Zhang
Keyword(s):  
Residual Body ◽  
C Elegans ◽  
Mediate Cell ◽  
Cell Corpse ◽  
Cell Corpse Clearance

scholarly journals Residual body removal during spermatogenesis in C. elegans requires genes that mediate cell corpse clearance

2012 ◽  
Vol 125 (24) ◽  
pp. e1-e1
Author(s):  
J. Huang ◽  
H. Wang ◽  
Y. Chen ◽  
X. Wang ◽  
H. Zhang
Keyword(s):  
Residual Body ◽  
C Elegans ◽  
Mediate Cell ◽  
Cell Corpse ◽  
Cell Corpse Clearance

scholarly journals Genes required for the engulfment of cell corpses during programmed cell death in Caenorhabditis elegans.

Genetics ◽  
1991 ◽  
Vol 129 (1) ◽  
pp. 79-94 ◽  
Author(s):  
R E Ellis ◽  
D M Jacobson ◽  
H R Horvitz
Keyword(s):  
Cell Death ◽  
Caenorhabditis Elegans ◽  
Programmed Cell Death ◽  
Nematode Caenorhabditis Elegans ◽  
Electron Microscopic ◽  
New Genes ◽  
Microscopic Studies ◽  
A Cell ◽  
Cell Corpse ◽  
Dying Cells

Abstract After programmed cell death, a cell corpse is engulfed and quickly degraded by a neighboring cell. For degradation to occur, engulfing cells must recognize, phagocytose and digest the corpses of dying cells. Previously, three genes were known to be involved in eliminating cell corpses in the nematode Caenorhabditis elegans: ced-1, ced-2 and nuc-1. We have identified five new genes that play a role in this process: ced-5, ced-6, ced-7, ced-8 and ced-10. Electron microscopic studies reveal that mutations in each of these genes prevent engulfment, indicating that these genes are needed either for the recognition of corpses by other cells or for the initiation of phagocytosis. Based upon our study of double mutants, these genes can be divided into two sets. Animals with mutations in only one of these sets of genes have relatively few unengulfed cell corpses. By contrast, animals with mutations in both sets of genes have many unengulfed corpses. These observations suggest that these two sets of genes are involved in distinct and partially redundant processes that act in the engulfment of cell corpses.

scholarly journals The small GTPase Rab2 functions in the removal of apoptotic cells in Caenorhabditis elegans

2008 ◽  
Vol 180 (2) ◽  
pp. 357-373 ◽  
Author(s):  
Paolo M. Mangahas ◽  
Xiaomeng Yu ◽  
Kenneth G. Miller ◽  
Zheng Zhou
Keyword(s):  
Caenorhabditis Elegans ◽  
Time Lapse ◽  
Cell Types ◽  
Small Gtpase ◽  
Dominant Negative ◽  
Apoptotic Cells ◽  
Loss Of Function ◽  
Guanosine Triphosphatase ◽  
Cell Corpse ◽  
Different Cell Types

We identify here a novel class of loss-of-function alleles of uncoordinated locomotion(unc)-108, which encodes the Caenorhabditis elegans homologue of the mammalian small guanosine triphosphatase Rab2. Like the previously isolated dominant-negative mutants, unc-108 loss-of-function mutant animals are defective in locomotion. In addition, they display unique defects in the removal of apoptotic cells, revealing a previously uncharacterized function for Rab2. unc-108 acts in neurons and engulfing cells to control locomotion and cell corpse removal, respectively, indicating that unc-108 has distinct functions in different cell types. Using time-lapse microscopy, we find that unc-108 promotes the degradation of engulfed cell corpses. It is required for the efficient recruitment and fusion of lysosomes to phagosomes and the acidification of the phagosomal lumen. In engulfing cells, UNC-108 is enriched on the surface of phagosomes. We propose that UNC-108 acts on phagosomal surfaces to promote phagosome maturation and suggest that mammalian Rab2 may have a similar function in the degradation of apoptotic cells.

scholarly journals An RNAi screen of the kinome in epithelial follicle cells of the Drosophila melanogaster ovary reveals genes required for proper germline death and clearance

2021 ◽  
Vol 11 (2) ◽  
Author(s):  
Diane P V Lebo ◽  
Alice Chirn ◽  
Jeffrey D Taylor ◽  
Andre Levan ◽  
Valentina Doerre Torres ◽  
...  
Keyword(s):  
Cell Death ◽  
Drosophila Melanogaster ◽  
Follicle Cells ◽  
Multiple Time ◽  
Cell Clearance ◽  
Germline Cells ◽  
Multiple Time Points ◽  
Cell Corpse ◽  
Cell Corpse Clearance ◽  
Drosophila Ovary

Abstract Programmed cell death and cell corpse clearance are an essential part of organismal health and development. Cell corpses are often cleared away by professional phagocytes such as macrophages. However, in certain tissues, neighboring cells known as nonprofessional phagocytes can also carry out clearance functions. Here, we use the Drosophila melanogaster ovary to identify novel genes required for clearance by nonprofessional phagocytes. In the Drosophila ovary, germline cells can die at multiple time points. As death proceeds, the epithelial follicle cells act as phagocytes to facilitate the clearance of these cells. We performed an unbiased kinase screen to identify novel proteins and pathways involved in cell clearance during two death events. Of 224 genes examined, 18 demonstrated severe phenotypes during developmental death and clearance while 12 demonstrated severe phenotypes during starvation-induced cell death and clearance, representing a number of pathways not previously implicated in phagocytosis. Interestingly, it was found that several genes not only affected the clearance process in the phagocytes, but also non-autonomously affected the process by which germline cells died. This kinase screen has revealed new avenues for further exploration and investigation.

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