Tyrosine cross-linking of extracellular matrix is catalyzed by Duox, a multidomain oxidase/peroxidase with homology to the phagocyte oxidase subunit gp91 phox

Citation
Wa. Edens et al., Tyrosine cross-linking of extracellular matrix is catalyzed by Duox, a multidomain oxidase/peroxidase with homology to the phagocyte oxidase subunit gp91 phox, J CELL BIOL, 154(4), 2001, pp. 879-891
Citations number
66
Categorie Soggetti
Cell & Developmental Biology
Journal title
JOURNAL OF CELL BIOLOGY
ISSN journal
00219525 → ACNP
Volume
154
Issue
4
Year of publication
2001
Pages
879 - 891
Database
ISI
SICI code
0021-9525(20010820)154:4<879:TCOEMI>2.0.ZU;2-P
Abstract
High molecular weight homologues of gp91 phox, the superoxide-generating su bunit of phagocyte nicotinamide adenine dinucleotide phosphate (NADPH)-oxid ase, have been identified in human (h) and Caenorhahditis elegans (Ce), and are termed Duox for "dual oxidase" because they have both a peroxidase hom ology domain and a gp91 phox domain. A topology model predicts that the enz yme will utilize cytosolic NADPH to generate reactive oxygen, but the funct ion of the ecto peroxidase domain was unknown. Ce-Duox1 is expressed in hyp odermal cells underlying the cuticle of larval animals. To investigate func tion, RNA interference (RNAi) was carried out in C. elegans. RNAi animals s howed complex phenotypes similar to those described previously in mutations in collagen biosynthesis that are known to affect the cuticle, an extracel lular matrix. Electron micrographs showed gross abnormalities in the cuticl e of RNAi animals. In cuticle, collagen and other proteins are cross-linked via di- and trityrosine linkages, and these linkages were absent in RNAi a nimals. The expressed peroxidase domains of both Ce-Duox1 and h-Duox showed peroxidase activity and catalyzed crosslinking of free tyrosine ethyl este r. Thus, Ce-Duox catalyzes the cross-linking of tyrosine residues involved in the stabilization of cuticular extracellular matrix.