title: Distinct Developmental Functions of Prostasin (CAP1/PRSS8) Zymogen and Activated Prostasin.
abstract: The membrane-anchored serine prostasin (CAP1/PRSS8) is essential for barrier acquisition of the interfollicular epidermis and for normal hair follicle development. Consequently, prostasin null mice die shortly after birth. Prostasin is found in two forms in the epidermis: a one-chain zymogen and a two-chain proteolytically active form, generated by matriptase-dependent activation site cleavage. Here we used gene editing to generate mice expressing only activation site cleavage-resistant (zymogen-locked) endogenous prostasin. Interestingly, these mutant mice displayed normal interfollicular epidermal development and postnatal survival, but had defects in whisker and pelage hair formation. These findings identify two distinct in vivo functions of epidermal prostasin: a function in the interfollicular epidermis, not requiring activation site cleavage, that can be mediated by the zymogen-locked version of prostasin and a proteolysis-dependent function of activated prostasin in hair follicles, dependent on zymogen conversion by matriptase.
authors.affiliation: From the Proteases and Tissue Remodeling Section, Oral and Pharyngeal Cancer Branch, NIDCR, National Institutes of Health, Bethesda, Maryland 20892, the Section for Molecular Disease Biology, Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark, and.
authors.forename: Stine
authors.initials: S
authors.lastname: Friis
authors.affiliation: From the Proteases and Tissue Remodeling Section, Oral and Pharyngeal Cancer Branch, NIDCR, National Institutes of Health, Bethesda, Maryland 20892, the Center for Cancer Immune Therapy, Copenhagen University Hospital Herlev, DK-2730 Herlev, Denmark.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Madsen
authors.affiliation: From the Proteases and Tissue Remodeling Section, Oral and Pharyngeal Cancer Branch, NIDCR, National Institutes of Health, Bethesda, Maryland 20892, thomas.bugge@nih.gov.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Bugge
mesh_terms: D000818:Animals; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000235:genetics / Q000378:metabolism*; D018859:Hair Follicle / Q000201:enzymology*; D051379:Mice; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D000099271:Prostasin
chemical_list: D004792:Enzyme Precursors; D012697:Serine Endopeptidases; D000099271:Prostasin; C485595:matriptase
keywords: enzyme catalysis; enzyme mechanism; epidermal development; epithelium; pericellular proteolysis; proteolysis; serine protease