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The initiator caspase, caspase‐10β, and the BH‐3‐only molecule, Bid, demonstrate evolutionary conservation in Xenopus of their pro‐apoptotic activities in the extrinsic and intrinsic pathways
Author(s) -
Kominami Katsuya,
Takagi Chiyo,
Kurata Tomoko,
Kitayama Atsushi,
Nozaki Masami,
Sawasaki Tatsuya,
Kuida Keisuke,
Endo Yaeta,
Manabe Noboru,
Ueno Naoto,
Sakamaki Kazuhiro
Publication year - 2006
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2006.00983.x
Subject(s) - biology , xenopus , microbiology and biotechnology , nlrp1 , apoptosis , caspase , caspase 9 , caspase 2 , programmed cell death , cytochrome c , caspase 8 , signal transduction , microinjection , intrinsic apoptosis , caspase 3 , mitochondrion , genetics , gene
Two major apoptotic signaling pathways have been defined in mammals, the extrinsic pathway, initiated by ligation of death receptors, and the intrinsic pathway, triggered by cytochrome c release from mitochondria. Here, we identified and characterized the Xenopus homologs of caspase‐10 (xCaspase‐10β), a novel initiator caspase, and Bid (xBid), a BH3‐only molecule of the Bcl‐2 family involved in both the extrinsic and intrinsic pathways. Exogenous expression of these molecules induced apoptosis of mammalian cells. By biochemical and cytological analyses, we clarified that xCaspase‐10β and xBid exhibit structural and functional similarities to their mammalian orthologues. We also detected xCaspase‐10β and xBid transcripts during embryogenesis by whole‐mount in situ hybridization and RT‐PCR analysis. Microinjection of mRNA encoding a protease‐defect xCaspase‐10β mutant into embryos resulted in irregular development. Enforced expression of active xBid induced cell death in developing embryos. Using transgenic frogs established to allow monitoring of caspase activation in vivo, we confirmed that this form of cell death is caspase‐dependent apoptosis. Thus, we demonstrated that the machinery governing the extrinsic and intrinsic apoptotic pathways are already established in Xenopus embryos. Additionally, we propose that the functions of the initiator caspase and BH3‐only molecule are evolutionarily conserved in vertebrates, functioning during embryonic development.