Conserved function of the matriptase-prostasin proteolytic cascade during epithelial morphogenesis

Extracellular matrix (ECM) assembly and remodelling is critical during development and organ morphogenesis. Dysregulation of ECM is implicated in many pathogenic conditions, including cancer. The type II transmembrane serine protease matriptase and the serine protease prostasin are key factors in a...

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Bibliographic Details
Published in:PLoS genetics 2019-01, Vol.15 (1), p.e1007882-e1007882
Main Authors: Drees, Leonard, Königsmann, Tatiana, Jaspers, Martin H J, Pflanz, Ralf, Riedel, Dietmar, Schuh, Reinhard
Format: Article
Language:English
Subjects:
Animals
Biology and Life Sciences
Carrier Proteins - genetics
Cell Differentiation - genetics
Chemistry
Chitin - genetics
Drosophila
Drosophila melanogaster - genetics
Drosophila melanogaster - growth & development
Drosophila Proteins - genetics
Endopeptidases - genetics
Epithelial Cells - metabolism
Epithelium - growth & development
Extracellular matrix
Extracellular Matrix - genetics
Extracellular Matrix Proteins - genetics
Gases
Gene expression
Humans
Insects
Invertebrates
Morphogenesis
Morphogenesis - genetics
Mutation
Observations
Physical Sciences
Physiological aspects
Polymerization
Proenzymes
Proteases
Protein Domains - genetics
Proteins
Proteolysis
Research and Analysis Methods
Serine
Serine Endopeptidases - genetics
Serine proteinase
Signal Transduction
Thrombin
Zona pellucida
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Summary:Extracellular matrix (ECM) assembly and remodelling is critical during development and organ morphogenesis. Dysregulation of ECM is implicated in many pathogenic conditions, including cancer. The type II transmembrane serine protease matriptase and the serine protease prostasin are key factors in a proteolytic cascade that regulates epithelial ECM differentiation during development in vertebrates. Here, we show by rescue experiments that the Drosophila proteases Notopleural (Np) and Tracheal-prostasin (Tpr) are functional homologues of matriptase and prostasin, respectively. Np mediates morphogenesis and remodelling of apical ECM during tracheal system development and is essential for maintenance of the transepithelial barrier function. Both Np and Tpr degrade the zona pellucida-domain (ZP-domain) protein Dumpy, a component of the transient tracheal apical ECM. Furthermore, we demonstrate that Tpr zymogen and the ZP domain of the ECM protein Piopio are cleaved by Np and matriptase in vitro. Our data indicate that the evolutionarily conserved ZP domain, present in many ECM proteins of vertebrates and invertebrates, is a novel target of the conserved matriptase-prostasin proteolytic cascade.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1007882