The let-268 locus of Caenorhabditis elegans encodes a procollagen lysyl hydroxylase that is essential for type IV collagen secretion.
Basement membranes are thin sheets of specialized extracellular matrix molecules that are important for supplying mechanical support and for providing an interactive surface for cell morphology. Prior to secretion and assembly, basement membrane molecules undergo intracellular processing, which is essential for their function. We have identified several mutations in a procollagen processing enzyme, lysyl hydroxylase (let-268). The Caenorhabditis elegans lysyl hydroxylase is highly similar to the vertebrate lysyl hydroxylase, containing all essential motifs required for enzymatic activity, and is the only lysyl hydroxylase found in the C. elegans sequenced genome. In the absence of C. elegans lysyl hydroxylase, type IV collagen is expressed; however, it is retained within the type IV collagen-producing cells. This observation indicates that in let-268 mutants the processing and secretion of type IV collagen is disrupted. Our examination of the body wall muscle in these mutant animals reveals normal myofilament assembly prior to contraction. However, once body wall muscle contraction commences the muscle cells separate from the underlying epidermal layer (the hypodermis) and the myofilaments become disorganized. These observations indicate that type IV collagen is required in the basement membrane for mechanical support and not for organogenesis of the body wall muscle.
Norman
K R
KR
Department of Zoology, University of British Columbia, Vancouver, British Columbia, V6T 1Z4, Canada.
Moerman
D G
DG
D008841:Actin Cytoskeleton / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001485:Basement Membrane / Q000254:growth & development; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000235:genetics* / Q000254:growth & development; D002874:Chromosome Mapping; D003094:Collagen / Q000096:biosynthesis; D015870:Gene Expression; D017238:Genes, Helminth; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009119:Muscle Contraction; D009154:Mutation; D011347:Procollagen / Q000378:metabolism; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
D019812:Heparan Sulfate Proteoglycans; D011347:Procollagen; C071927:perlecan; D003094:Collagen; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase