Abstract
In Caenorhabditis elegans, apoptosis in germ cells is mediated by the same core apoptotic machinery that controls apoptosis in somatic cells. These include the CED-3 caspase, the CED-3 activator CED-4, and the cell death inhibitor CED-9. However, germline apoptosis also differs from somatic apoptosis in its regulation. We found that CSP-3, a caspase homolog that blocks CED-3 autoactivation and apoptosis in somatic cells, does not affect apoptosis in germ cells. Interestingly, the second C. elegans caspase homolog, CSP-2, shares sequence similarity to both catalytic subunits of the CED-3 caspase, and surprisingly, contains a stretch of sequence that is almost identical to that of CSP-3. Unlike CSP-3 that acts specifically in somatic cells, loss of CSP-2 causes increased apoptosis only in germ cells, suggesting that CSP-2 is a germ cell-specific apoptosis inhibitor. Moreover, like CSP-3, CSP-2 associates with the CED-3 zymogen and inhibits its autoactivation, but does not inhibit CED-4-induced CED-3 activation or the activity of the activated CED-3 protease. Thus, two different C. elegans caspase homologs use the same mechanism to prevent caspase autoactivation and apoptosis in different tissues, suggesting that this could be a generally applicable strategy for regulating caspase activation and apoptosis.
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Abbreviations
- AA:
-
amino acid
- GFP:
-
green fluorescent protein
- L1-L4:
-
larval stages 1-4
- N2:
-
wild-type C. elegans strains-Bristol isolate
- PCD:
-
programmed cell death
- RT-PCR:
-
reverse transcriptase polymerase chain reaction
- WT:
-
wild type
- CED:
-
cell death abnormal
- S.E.M:
-
standard error of the mean
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Acknowledgements
We thank N Pace for advice on phylogenetic analysis, Y Shi and members of the Xue laboratory for comments and discussions, L Yang, HW Yang, and CL Sun for technical support, S Shaham for cDNA clones, and M Driscoll (Rutgers University) for the bzIs8 strain. This work was supported by NIH R01 grants (GM059083 and GM079097) and a Burroughs Welcome Fund Award to DX and a grant from MEXT of Japan to SM. XG was supported by U Colorado Matching Grant to the SCR Training Grant (T32 GM08759).
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Geng, X., Zhou, Q., Kage-Nakadai, E. et al. Caenorhabditis elegans caspase homolog CSP-2 inhibits CED-3 autoactivation and apoptosis in germ cells. Cell Death Differ 16, 1385–1394 (2009). https://doi.org/10.1038/cdd.2009.88
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DOI: https://doi.org/10.1038/cdd.2009.88
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