title: Protein disulfide isomerase activity is essential for viability and extracellular matrix formation in the nematode Caenorhabditis elegans.
abstract: Protein disulfide isomerase (PDI) is a multifunctional protein required for many aspects of protein folding and transit through the endoplasmic reticulum. A conserved family of three PDIs has been functionally analysed using genetic mutants of the model organism Caenorhabditis elegans. PDI-1 and PDI-3 are individually non-essential, whereas PDI-2 is required for normal post-embryonic development. In combination, all three genes are synergistically essential for embryonic development in this nematode. Mutations in pdi-2 result in severe body morphology defects, uncoordinated movement, adult sterility, abnormal molting and aberrant collagen deposition. Many of these phenotypes are consistent with a role in collagen biogenesis and extracellular matrix formation. PDI-2 is required for the normal function of prolyl 4-hydroxylase, a key collagen-modifying enzyme. Site-directed mutagenesis indicates that the independent catalytic activity of PDI-2 may also perform an essential developmental function. PDI-2 therefore performs two critical roles during morphogenesis. The role of PDI-2 in collagen biogenesis can be restored following complementation of the mutant with human PDI.
authors.affiliation: Institute of Comparative Medicine, Veterinary Faculty, University of Glasgow, Bearsden Road, Glasgow, G61 1QH, Scotland, UK.
authors.forename: Alan D
authors.initials: AD
authors.lastname: Winter
authors.forename: Gillian
authors.initials: G
authors.lastname: McCormack
authors.forename: Antony P
authors.initials: AP
authors.lastname: Page
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D005109:Extracellular Matrix / Q000201:enzymology; D017238:Genes, Helminth; D005816:Genetic Complementation Test; D006801:Humans; D009154:Mutation; D010641:Phenotype; D019704:Protein Disulfide-Isomerases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D034622:RNA Interference
chemical_list: D029742:Caenorhabditis elegans Proteins; D003094:Collagen; D019704:Protein Disulfide-Isomerases