title: The astacin metalloprotease moulting enzyme NAS-36 is required for normal cuticle ecdysis in free-living and parasitic nematodes.
abstract: Nematodes represent one of the most abundant and species-rich groups of animals on the planet, with parasitic species causing chronic, debilitating infections in both livestock and humans worldwide. The prevalence and success of the nematodes is a direct consequence of the exceptionally protective properties of their cuticle. The synthesis of this cuticle is a complex multi-step process, which is repeated 4 times from hatchling to adult and has been investigated in detail in the free-living nematode, Caenorhabditis elegans. This process is known as moulting and involves numerous enzymes in the synthesis and degradation of the collagenous matrix. The nas-36 and nas-37 genes in C. elegans encode functionally conserved enzymes of the astacin metalloprotease family which, when mutated, result in a phenotype associated with the late-stage moulting defects, namely the inability to remove the preceding cuticle. Extensive genome searches in the gastrointestinal nematode of sheep, Haemonchus contortus, and in the filarial nematode of humans, Brugia malayi, identified NAS-36 but not NAS-37 homologues. Significantly, the nas-36 gene from B. malayi could successfully complement the moult defects associated with C. elegans nas-36, nas-37 and nas-36/nas-37 double mutants, suggesting a conserved function for NAS-36 between these diverse nematode species. This conservation between species was further indicated when the recombinant enzymes demonstrated a similar range of inhibitable metalloprotease activities.
authors.affiliation: Division of Infection and Immunity, Institute of Comparative Medicine, Faculty of Veterinary Medicine, University of Glasgow, Bearsden Road, Glasgow G611QH, UK.
authors.forename: Gillian
authors.initials: G
authors.lastname: Stepek
authors.forename: Gillian
authors.initials: G
authors.lastname: McCormack
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Birnie
authors.forename: Antony P
authors.initials: AP
authors.lastname: Page
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017178:Brugia malayi / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D018507:Gene Expression Regulation, Developmental; D017238:Genes, Helminth; D005816:Genetic Complementation Test; D006189:Haemonchus / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008666:Metalloendopeptidases / Q000235:genetics* / Q000378:metabolism; D045726:Metalloproteases / Q000235:genetics* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018978:Molting / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
chemical_list: D029742:Caenorhabditis elegans Proteins; D045726:Metalloproteases; C559120:NAS-36 protein, C elegans; C496520:NAS-37 protein, C elegans; D008666:Metalloendopeptidases; C071288:astacin