Collagen processing and cuticle formation is catalysed by the astacin metalloprotease DPY-31 in free-living and parasitic nematodes

Stepek, G., McCormack, G. and Page, A. P. (2010) Collagen processing and cuticle formation is catalysed by the astacin metalloprotease DPY-31 in free-living and parasitic nematodes. International Journal for Parasitology, 40(5), pp. 533-542. (doi: 10.1016/j.ijpara.2009.10.007) (PMID:19883650)

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Publisher's URL: http://dx.doi.org/10.1016/j.ijpara.2009.10.007

Abstract

The exoskeleton or cuticle performs many key roles in the development and survival of all nematodes. This structure is predominantly collagenous in nature and requires numerous enzymes to properly fold, modify, process and cross-link these essential structural proteins. The cuticle structure and its collagen components are conserved throughout the nematode phylum but differ from the collagenous matrices found in vertebrates. This structure, its formation and the enzymology of nematode cuticle collagen biogenesis have been elucidated in the free-living nematode Caenorhabditis elegans. The dpy-31 gene in C. elegans encodes a procollagen C-terminal processing enzyme of the astacin metalloprotease or bone morphogenetic protein class that, when mutated, results in a temperature-sensitive lethal phenotype associated with cuticle defects. In this study, orthologues of this essential gene have been identified in the phylogenetically diverse parasitic nematodes Haemonchus contortus and Brugia malayi. The DPY-31 protein is expressed in the gut and secretory system of C. elegans, a location also confirmed when a B. malayi transcriptional dpy-31 promoter-reporter gene fusion was expressed in C. elegans. Functional conservation between the nematode enzymes was supported by the fact that heterologous expression of the H. contortus dpy-31 orthologue in a C. elegans dpy-31 mutant resulted in the full rescue of the mutant body form. This interspecies conservation was further established when the recombinant nematode enzymes were found to have a similar range of inhibitable protease activities. In addition, the recombinant DPY-31 enzymes from both H. contortus and B. malayi were shown to efficiently process the C. elegans cuticle collagen SQT-3 at the correct C-terminal procollagen processing site.

Item Type:Articles
Keywords:Caenorhabditis elegans, haemonchus contortus, brugia malayi, astacin metalloprotease, BMP, development, cuticle
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Page, Professor Tony and McCormack, Ms Gillian and Stepek, Dr Gillian
Authors: Stepek, G., McCormack, G., and Page, A. P.
Subjects:Q Science > QL Zoology
Q Science > QH Natural history > QH345 Biochemistry
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:International Journal for Parasitology
Journal Abbr.:Int. j. parasitol.
Publisher:Elsevier on behalf of the Australian Society for Parasitology
ISSN:0020-7519
ISSN (Online):1879-0135
Published Online:31 October 2009
Copyright Holders:Copyright © 2009 Australian Society for Parasitology
First Published:First published in International Journal for Parasitology 40(5):533-542
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
403961Moulting and hatching in nematodes - the role of astacin metalloproteases as potential anti-nematode targetsAntony PageBiotechnology and Biological Sciences Research Council (BBSRC)BB/D000661/1Infection 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