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Distinct Developmental Functions of Prostasin (CAP1/PRSS8) Zymogen and Activated Prostasin

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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 post-natal 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.

OriginalsprogEngelsk
TidsskriftJournal of Biological Chemistry
Vol/bind291
Udgave nummer6
Sider (fra-til):2577-8
ISSN0021-9258
DOI
StatusUdgivet - feb. 2015

ID: 45980797