A cathepsin L protease essential for Caenorhabditis elegans embryogenesis is functionally conserved in parasitic nematodes.
Proteolytic enzymes are involved in processes important to development and survival of many organisms. Parasite proteases are considered potential targets of parasite control yet, for most, their precise physiological functions are unknown. Validation of potential targets requires analysis of function. We have recently identified a cathepsin L (CPL) cysteine protease, Ce-CPL-1, which is essential for embryonic development of the free-living nematode Caenorhabditis elegans. We now show that CPL genes closely related to Ce-cpl-1 are expressed in the animal parasitic nematodes Haemonchus contortus, Dictyocaulus viviparus, Teladorsagia circumcincta, Ancylostoma caninum and Ascaris suum, as well as in plant parasitic nematodes. The similarities in gene structure and encoded amino acid sequence indicate that the parasite and C. elegans CPLs are homologous enzymes. We demonstrate functional compensation of the loss of C. elegans cpl-1 by transgenic expression of the H. contortus cpl-1 gene, rescuing the embryonic lethality. These genes may therefore be orthologues, sharing the same function in both species. Targeting of this enzyme has potential in inhibiting development and transmission of parasitic nematodes. In addition, the role of CPL is important to our understanding of nematode development.
Britton
Collette
C
Wellcome Centre for Molecular Parasitology, University of Glasgow, Scotland, UK. cb32n@udcf.gla.ac.uk
Murray
Linda
L
D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000201:enzymology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D056668:Cathepsin L; D002403:Cathepsins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017124:Conserved Sequence; D003546:Cysteine Endopeptidases; D017238:Genes, Helminth / Q000235:genetics; D005816:Genetic Complementation Test; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009348:Nematoda / Q000196:embryology* / Q000201:enzymology* / Q000235:genetics; D010641:Phenotype; D010802:Phylogeny; D012330:RNA, Double-Stranded / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D029742:Caenorhabditis elegans Proteins; D012330:RNA, Double-Stranded; D002403:Cathepsins; D003546:Cysteine Endopeptidases; C466023:CPL-1 protein, C elegans; C534281:CTSL protein, human; D056668:Cathepsin L