RRC ID 3645
Author Winter AD, McCormack G, Page AP.
Title Protein disulfide isomerase activity is essential for viability and extracellular matrix formation in the nematode Caenorhabditis elegans.
Journal Dev. Biol.
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.
Volume 308(2)
Pages 449-61
Published 2007-8-15
DOI 10.1016/j.ydbio.2007.05.041
PII S0012-1606(07)01111-6
PMID 17586485
MeSH Animals Animals, Genetically Modified Caenorhabditis elegans / embryology* Caenorhabditis elegans / enzymology* Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Collagen / genetics Collagen / metabolism Evolution, Molecular Extracellular Matrix / enzymology Genes, Helminth Genetic Complementation Test Humans Mutation Phenotype Protein Disulfide-Isomerases / antagonists & inhibitors Protein Disulfide-Isomerases / chemistry Protein Disulfide-Isomerases / genetics Protein Disulfide-Isomerases / metabolism* Protein Structure, Tertiary RNA Interference
IF 2.936
Times Cited 20
C.elegans tm0689