Journal
ELIFE
Volume 4, Issue -, Pages -Publisher
ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.08887
Keywords
-
Categories
Funding
- Fondazione Telethon [TCR08006, GGP14263]
- Ministero della Salute [RF-2010-2319394]
- Swiss National Science Foundation [31003A-144198/1, 310030-146490, 32003B-149309]
- National Center of Competence in Research [Kidney.Ch]
- Fonds National de la Recherche Luxembourg [6903109]
- European Commission [246539, 305608]
- Fonds De La Recherche Scientifique - FNRS
- Fonds De La Recherche Scientifique Medicale
- Gebert Ruf Stiftung [GRS-038/12]
- Swedish Research Council [2012-5093]
- Goran Gustafsson Foundation for Research in Natural Sciences and Medicine
- European Research Council under European Union [ERC 260759]
- Swiss National Science Foundation (SNF) [31003A_144198, 32003B_149309] Funding Source: Swiss National Science Foundation (SNF)
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available