CGC Bibliography Paper 5704

The Caenorhabditis elegans ERp60 homolog protein disulfide isomerase-3 has disulfide isomerase and transglutaminase-like cross-linking activity and is involved in the maintenance of body morphology.

Eschenlauer SCP, Page AP

Medline:

12424233

Citation:

Journal of Biological Chemistry 278: 4227-4237 2003

Type:

ARTICLE

Genes:

dpy-3 dpy-5 dpy-7 dpy-8 dpy-10 dpy-11 dpy-13 dpy-18 pdi-3 phy-2 phy-3 sqt-1 sqt-3 unc-119

Abstract:

A novel protein disulfide isomerase gene, pdi-3, was isolated from the nematode Caenorhabditis elegans. This gene encodes an enzyme related to the ERp60 class of thioredoxin proteins and was found to exhibit unusual enzymatic properties. Recombinant protein displayed both disulfide bond isomerase activity and calcium-dependent transglutaminase-like cross-linking activity. The pdi-3 transcript was developmentally constitutively expressed, and the encoded protein is present in many tissues including the gut and the hypodermis. The nematode hypodermis synthesizes the essential collagenous extracellular matrix (ECM) called the cuticle. Transcript disruption via double-stranded RNA interference resulted in dramatic and specific synthetic phenotypes in several C. elegans mutant alleles with weakened cuticles: sqt-3(e2117), dpy-18(e364, ok162, and bx26). These nematodes displayed severe dumpy phenotypes and disrupted lateral alae, a destabilized cuticle and abnormal male and hermaphrodite tail morphologies. These defects were confirmed to be consistent with hypodermal seam cell abnormalities and corresponded with the severe disruption of a cuticle collagen. Wild type nematodes did not exhibit observable morphological defects; however, cuticle collagen localization was mildly disrupted following pdi-3 RNA interference. The unusual thioredoxin enzyme, protein disulfide isomerase-3, may therefore play a role in ECM assembly. This enzyme is required for the proper maintenance of postembryonic body shape in strains with a weakened cuticle, perhaps through ECM stabilization via cross-linking activity, disulfide isomerase protein folding activity, protein disulfide isomerase-chaperone activity