Abstract:
: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.
journal_name
Elifejournal_title
eLifeauthors
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 Ldoi
10.7554/eLife.08887subject
Has Abstractpub_date
2015-12-17 00:00:00pages
e08887issn
2050-084Xpii
08887journal_volume
4pub_type
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