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 mole cules that are important for supplying mechanical support and for providing an interactive surface for cell morphology. Prior to secretion and assembl y, basement membrane molecules undergo intracellular processing, which is e ssential for their function. We have identified several mutations in a proc ollagen processing enzyme, lysyl hydroxylase (let-268). The Caenorhabditis elegans lysyl hydroxylase is highly similar to the vertebrate lysyl hydroxy lase, 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 i n these mutant animals reveals normal myofilament assembly prior to contrac tion. However, once body wall muscle contraction commences the muscle cells separate from the underlying epidermal layer (the hypodermis) and the myof ilaments become disorganized. These observations indicate that type IV coll agen is required in the basement membrane for mechanical support and not fo r organogenesis of the body wall muscle. (C) 2000 Academic Press.