RRC ID 54398
Author Drees L, Königsmann T, Jaspers MHJ, Pflanz R, Riedel D, Schuh R.
Title Conserved function of the matriptase-prostasin proteolytic cascade during epithelial morphogenesis.
Journal PLoS Genet
Abstract 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.
Volume 15(1)
Pages e1007882
Published 2019-1-1
DOI 10.1371/journal.pgen.1007882
PMID 30601807
PMC PMC6331135
MeSH Animals Carrier Proteins / genetics* Cell Differentiation / genetics Chitin / genetics Drosophila Proteins / genetics* Drosophila melanogaster / genetics Drosophila melanogaster / growth & development Endopeptidases / genetics* Epithelial Cells / metabolism Epithelium / growth & development* Extracellular Matrix / genetics Extracellular Matrix Proteins / genetics Humans Morphogenesis / genetics* Protein Domains / genetics Serine Endopeptidases / genetics* Signal Transduction
IF 5.175
Times Cited 2
Drosophila CAS-0003 DGRC#115238