title: Biosynthesis and enzymology of the Caenorhabditis elegans cuticle: identification and characterization of a novel serine protease inhibitor.
abstract: Caenorhabditis elegans represents an excellent model in which to dissect the biosynthesis and assembly of the nematode cuticle. A sequenced genome, straightforward transgenesis, available mutants and practical genome-wide RNAi approaches provide an invaluable toolkit in the characterization of cuticle components. We have performed a targeted RNAi screen in an attempt to identify components of the cuticle collagen biosynthetic pathway. Collagen biosynthesis and cuticle assembly are multi-step processes that involve numerous key enzymes involved in post-translational modification, trimer folding, procollagen processing and subsequent cross-linking stages. For many of these steps, the modifications and the enzymes are unique to nematodes and may represent attractive targets for the control of parasitic nematodes. A novel serine protease inhibitor was uncovered during our targeted screen, which is involved in collagen maturation, proper cuticle assembly and the moulting process. We have confirmed a link between this inhibitor and the previously uncharacterised bli-5 locus in C. elegans. The mutant phenotype, spatial expression pattern and the over-expression phenotype of the BLI-5 protease inhibitor and their relevance to collagen biosynthesis are discussed.
authors.affiliation: Faculty of Veterinary Medicine, Institute of Comparative Medicine, University of Glasgow, Bearsden Road, Glasgow G61 1QH, UK. a.page@vet.gla.ac.uk
authors.forename: Antony P
authors.initials: AP
authors.lastname: Page
authors.forename: Gillian
authors.initials: G
authors.lastname: McCormack
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Birnie
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D029742:Caenorhabditis elegans Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D003094:Collagen / Q000096:biosynthesis*; D018509:DNA, Helminth / Q000235:genetics; D005786:Gene Expression Regulation; D008854:Microscopy, Electron; D010641:Phenotype; D017354:Point Mutation; D034622:RNA Interference; D015842:Serine Proteinase Inhibitors / Q000502:physiology*; D015843:Serpins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology
chemical_list: C519116:BLI-5 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D018509:DNA, Helminth; D015842:Serine Proteinase Inhibitors; D015843:Serpins; D003094:Collagen