The kunitz domain protein BLI-5 plays a functionally conserved role in cuticle formation in a diverse range of nematodes

MLT-10 Defines a Family of DUF644 and Proline-rich Repeat Proteins Involved in the Molting Cycle ofCaenorhabditis elegans

“…Consistent with that view, deformities in the ultrastructure of the underlying cuticle have been observed in particular molting-defective mutants (Hao et al , 2006). Moreover, certain enzymes involved in the biosynthesis of collagens and other ECM proteins are needed for the removal of larval cuticles, including the glycosyltransferase BUS-8, the peroxidases BLI-3 and MLT-7, and the protease BLI-5 (Edens et al , 2001; Davis et al , 2004; Frand et al , 2005; Page et al , 2006; Partridge et al , 2008; Thein et al , 2009; Stepek et al , 2010). In theory, progress through ecdysis might depend on physiological feedback on the status of the new exoskeleton.…”

Enzymology of the nematode cuticle: A potential drug target?

“…Mutation of bli-5 resulted in a blistered cuticle, while overexpression produced a severe moulting phenotype (Page et al, 2006). Protein annotation suggested BLI-5 was a protease inhibitor; however biochemical characterisation of C. elegans BLI-5 revealed that it activated, rather than inhibited, serine protease activity (Stepek et al, 2010b). BLI-5 orthologues from the parasitic nematodes Haemonchus contortus and B. malayi were both able to complement the C. elegans bli-5 mutant and both also activated serine protease activity in vitro (Stepek et al, 2010b).…”

“…Protein annotation suggested BLI-5 was a protease inhibitor; however biochemical characterisation of C. elegans BLI-5 revealed that it activated, rather than inhibited, serine protease activity (Stepek et al, 2010b). BLI-5 orthologues from the parasitic nematodes Haemonchus contortus and B. malayi were both able to complement the C. elegans bli-5 mutant and both also activated serine protease activity in vitro (Stepek et al, 2010b). The biochemical characterisation and phenotypic similarity between bli-5 and -4 mutants suggests BLI-5 might regulate BLI-4 (Stepek et al, 2010b).…”

“…BLI-5 orthologues from the parasitic nematodes Haemonchus contortus and B. malayi were both able to complement the C. elegans bli-5 mutant and both also activated serine protease activity in vitro (Stepek et al, 2010b). The biochemical characterisation and phenotypic similarity between bli-5 and -4 mutants suggests BLI-5 might regulate BLI-4 (Stepek et al, 2010b). In support of this, both bli-5 and bli-4 were found to share common temporal and spatial expression patterns and combined bli-4 / bli-5 RNAi produced a variable but synergistic effect (Stepek et al, 2010b).…”

“…The biochemical characterisation and phenotypic similarity between bli-5 and -4 mutants suggests BLI-5 might regulate BLI-4 (Stepek et al, 2010b). In support of this, both bli-5 and bli-4 were found to share common temporal and spatial expression patterns and combined bli-4 / bli-5 RNAi produced a variable but synergistic effect (Stepek et al, 2010b). …”