Protein disulfide isomerase activity is essential for viability and extracellular matrix formation in the nematode Caenorhabditis elegans.

Winter, A. D., McCormack, G. and Page, A. P. (2007) Protein disulfide isomerase activity is essential for viability and extracellular matrix formation in the nematode Caenorhabditis elegans. Developmental Biology, 308(2), pp. 449-461. (doi: 10.1016/j.ydbio.2007.05.041)

[img] Text
Page24944.pdf

573kB

Publisher's URL: http://dx.doi.org/10.1016/j.ydbio.2007.05.041

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 have been functionally analysed using genetic mutants of the model organism Caenorhabditis elegans. PDI-1 and PDI-3 are individually nonessential, 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 partially restored following complementation of the mutant with human PDI.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McCormack, Ms Gillian and Page, Professor Tony and Winter, Dr Alan
Authors: Winter, A. D., McCormack, G., and Page, A. P.
Subjects:Q Science > QH Natural history > QH345 Biochemistry
Q Science > QH Natural history > QH426 Genetics
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Research Group:Page Group
Journal Name:Developmental Biology
Publisher:Elsevier
ISSN:0012-1606
ISSN (Online):1095-564X
Published Online:05 June 2007
Copyright Holders:Copyright © 2007 Elsevier
First Published:First published in Developmental Biology 308(2):449-461
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher
Related URLs:

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
229991The Molecular Enzymology of Collagen Assembly and Post-Translational Modification: a Nematode Model SystemAntony PageMedical Research Council (MRC)G117/290Infection Immunity and Inflammation Life Sciences
229993The Molecular Enzymology of Collagen Assembly and Post-Translational Modification: a Nematode Model SystemAntony PageMedical Research Council (MRC)G117/476III - PARASITOLOGY