The lysosomal cathepsin protease CPL-1 plays a leading role in phagosomal degradation of apoptotic cells in Caenorhabditis elegans.
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.
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, ChinaGraduate University of Chinese Academy of Sciences, Beijing 100109, China.
Meng
M
Xu
National Institute of Biological Sciences, Beijing 102206, China.
Yubing
Y
Liu
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, ChinaGraduate University of Chinese Academy of Sciences, Beijing 100109, China.
Liyuan
L
Zhao
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, ChinaGraduate University of Chinese Academy of Sciences, Beijing 100109, China.
Qiwen
Q
Gan
National Institute of Biological Sciences, Beijing 102206, China.
Xiaochen
X
Wang
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China clyang@genetics.ac.cn.
Chonglin
C
Yang
D000818:Animals; D017209:Apoptosis; D017173:Caenorhabditis elegans / Q000166:cytology / Q000201:enzymology; D029742:Caenorhabditis elegans Proteins / Q000502:physiology*; D056668:Cathepsin L / Q000502:physiology*; D015870:Gene Expression; D010588:Phagosomes / Q000201:enzymology*; D021381:Protein Transport; D059748:Proteolysis
D029742:Caenorhabditis elegans Proteins; C466023:CPL-1 protein, C elegans; D056668:Cathepsin L