title: The kunitz domain protein BLI-5 plays a functionally conserved role in cuticle formation in a diverse range of nematodes.
abstract: The cuticle of parasitic nematodes performs many critical functions and is essential for proper development and for protection from the host immune response. The biosynthesis, assembly, modification and turnover of this exoskeleton have been most extensively studied in the free-living nematode, Caenorhabditis elegans, where it represents a complex multi-step process involving a whole suite of enzymes. The biosynthesis of the cuticle has an additional level of complexity, as many of the enzymes also require additional proteins to aid their activation and selective inhibition. Blister-5 (BLI-5) represents a protein with a kunitz-type serine protease interacting domain and is involved in cuticle collagen biosynthesis in C. elegans, through its interaction with subtilisin-like processing enzymes (such as BLI-4). Mutation of the bli-5 gene causes blistering of the collagenous adult cuticle. Homologues of BLI-5 have been identified in several parasitic species that span different nematode clades. In this study, we molecularly and biochemically characterize BLI-5 homologues from the clade V nematodes C. elegans and Haemonchus contortus and from the clade III filarial nematode Brugia malayi. The nematode BLI-5 orthologues possess a shared domain structure and perform similar in vitro and in vivo functions, performing important proteolytic enzyme functions. The results demonstrate that the bli-5 genes from these diverse parasitic nematodes are able to complement a C. elegansbli-5 mutant and thereby support the use of the C. elegans model system to examine gene function in the experimentally less-amenable parasitic species.
authors.affiliation: Institute of Comparative Medicine, University of Glasgow, Scotland, United Kingdom.
authors.forename: Gillian
authors.initials: G
authors.lastname: Stepek
authors.forename: Gillian
authors.initials: G
authors.lastname: McCormack
authors.forename: Antony P
authors.initials: AP
authors.lastname: Page
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017178:Brugia malayi / Q000737:chemistry / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000737:chemistry / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003094:Collagen / Q000096:biosynthesis; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental; D006189:Haemonchus / Q000737:chemistry / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D015843:Serpins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: C519116:BLI-5 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D015843:Serpins; D003094:Collagen