The lysosomal cathepsin protease CPL-1 plays a leading role in phagosomal degradation of apoptotic cells in Caenorhabditis elegans
| 作者： |
Meng Xu,Yubing Liu,Liyuan Zhao,Qiwen Gan,Xiaochen Wang,and Chonglin Yang |
| 刊物名称： |
Molecular Biology of the Cell |
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| 发表年度： |
2014-06-12 |
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| 摘要： |
During programmed cell death, the clearance of apoptotic cells is achieved by their phagocytosis and delivery to lysosomes for destruction in engulfing cells. The role of lysosomal proteases in cell corpse destruction is, however, not understood. Here we report the identification of the lysosomal cathepsin CPL-1 as an indispensable protease for apoptotic cell removal in C. elegans. We found that loss of cpl-1 function led to a strong accumulation of germ cell corpses, which resulted 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. Importantly, we found that phagosomal recruitment and incorporation of CPL-1 occurs prior to the digestion of cell corpses, which depends on factors required for phagolysosome formation. Using RNAi, we further examined the role of other candidate lysosomal proteases in cell corpse clearance but found that they did 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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