C. elegans caspase homolog CSP-2 inhibits CED-3 autoactivation and apoptosis in germ cells

• Published in: Cell death and differentiation Vol. 16; no. 10; pp. 1385 - 1394
• Main Authors: Geng, X, Zhou, QH, Kage-Nakadai, E, Shi, Y, Yan, N, Mitani, S, Xue, D
• Format: Journal Article
• Language: English
• Published: 03.07.2009
• ISSN: 1350-9047; 1476-5403
• DOI: 10.1038/cdd.2009.88

In C. 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 employ 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.