Characterization of caspases from Lepidoptera and their role in apoptosis

Courtiade, Juliette

Multicellular organisms need a tightly controlled regulation of cell proliferation and of cell specialization together with a controlled cell death to maintain their integrity. A family of evolutionarily conserved proteases, called caspases, plays a central role in regulating apoptosis in animals. The discovery of p35, a baculovirus caspase inhibitor, has led to the characterization of the first lepidopteran caspase, Sf-Caspase-1, from Spodoptera frugiperda. Studies on the Sf-Caspase-1 mode of activation suggested that apoptosis in Lepidoptera also requires a cascade of caspase activation, as demonstrated in many other species. We identified 66 sequences encoding putative caspases, distributed among 27 species. Phylogenetic analyses showed that Lepidoptera possess at least 5 caspases, for which we propose a unified nomenclature. According to their homology to their Drosophila counterparts and their primary structure, we proposed that Lep-Caspase-1, -2 and -3 are effector caspases, whereas Lep-Caspase-5 and -6 are putative initiators. The likely function of Lep-Caspase-4 remains unclear. We found that Caspase-1 and -2 have complementary expression profiles during larval development, suggesting a differential regulation. Caspase-3 and -6 are upregulated upon immune challenge, suggesting a role in the imd pathway. Caspase-5 is upregulated during pupation and upon induction with 20-hydroxyecdysone, supporting the hypothesis of Caspase-5 playing a similar role as Dronc in developmental apoptosis in Drosophila. In an attempt to obtain further insights into the molecular pathway underlying apoptosis in lepidopteran insects, we used 2D DIGE to identify 13 proteins, for which relative abundance was altered during apoptosis of H. armigera derived cells, induced by actinomycin D. Among these 13 proteins, we identified the putative effector Caspase-1, 3 chaperone proteins and several pro-apoptotic proteins, such as actin and a voltage dependant anion channel.

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Courtiade, Juliette: Characterization of caspases from Lepidoptera and their role in apoptosis. 2011.

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