The serine protease hepsin mediates urinary secretion and polymerisation of Zona Pellucida domain protein uromodulin.

Détails

Ressource 1Télécharger: BIB_57B27B8690E9.P001.pdf (4250.00 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_57B27B8690E9
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
The serine protease hepsin mediates urinary secretion and polymerisation of Zona Pellucida domain protein uromodulin.
Périodique
Elife
Auteur(s)
Brunati M., Perucca S., Han L., Cattaneo A., Consolato F., Andolfo A., Schaeffer C., Olinger E., Peng J., Santambrogio S., Perrier R., Li S., Bokhove M., Bachi A., Hummler E., Devuyst O., Wu Q., Jovine L., Rampoldi L.
ISSN
2050-084X (Electronic)
ISSN-L
2050-084X
Statut éditorial
Publié
Date de publication
2015
Peer-reviewed
Oui
Volume
4
Pages
e08887
Langue
anglais
Résumé
Uromodulin is the most abundant protein in the urine. It is exclusively produced by renal epithelial cells and it plays key roles in kidney function and disease. Uromodulin mainly exerts its function as an extracellular matrix whose assembly depends on a conserved, specific proteolytic cleavage leading to conformational activation of a Zona Pellucida (ZP) polymerisation domain. Through a comprehensive approach, including extensive characterisation of uromodulin processing in cellular models and in specific knock-out mice, we demonstrate that the membrane-bound serine protease hepsin is the enzyme responsible for the physiological cleavage of uromodulin. Our findings define a key aspect of uromodulin biology and identify the first in vivo substrate of hepsin. The identification of hepsin as the first protease involved in the release of a ZP domain protein is likely relevant for other members of this protein family, including several extracellular proteins, as egg coat proteins and inner ear tectorins.
Pubmed
Web of science
Open Access
Oui
Création de la notice
18/01/2016 11:30
Dernière modification de la notice
20/08/2019 14:11
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