The serine protease hepsin mediates urinary secretion and polymerisation of Zona Pellucida domain protein uromodulin
نویسندگان
چکیده
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.
منابع مشابه
Protease activity involvement in the passage of mammalian sperm through the zona pellucida.
The interaction between acrosome-reacted sperm and zona pellucida proteins is not yet fully understood. Serine protease acrosin and its zymogen proacrosin have been proposed to fulfill this function due to their capacity to bind zona pellucida glycoproteins. However, the molecular mechanism underlying this interaction has been merely speculative. Here we show that fucoidan (a sulfated polysacch...
متن کاملUromodulin , an Emerging Novel Pathway for Blood Pressure Regulation and Hypertension
Tamm–Horsfall protein was discovered in 1950 by Igor Tamm and Frank Horsfall, using a salt precipitation procedure to isolate a potent inhibitor of viral hemagglutination from urine. Muchmore and Decker, in 1985, isolated a glycoprotein (calling it uromodulin) with in vitro immunosuppressive properties from urine of pregnant women. In 1987, Pennica et al confirmed by cDNA analysis that uromodul...
متن کاملUromodulin, an emerging novel pathway for blood pressure regulation and hypertension.
Tamm–Horsfall protein was discovered in 1950 by Igor Tamm and Frank Horsfall, using a salt precipitation procedure to isolate a potent inhibitor of viral hemagglutination from urine. Muchmore and Decker, in 1985, isolated a glycoprotein (calling it uromodulin) with in vitro immunosuppressive properties from urine of pregnant women. In 1987, Pennica et al confirmed by cDNA analysis that uromodul...
متن کاملMutation of a conserved hydrophobic patch prevents incorporation of ZP3 into the zona pellucida surrounding mouse eggs.
Three glycoproteins (ZP1, ZP2, and ZP3) are synthesized in growing mouse oocytes and secreted to form an extracellular zona pellucida that mediates sperm binding and fertilization. Each has a signal peptide to direct it into a secretory pathway, a "zona" domain implicated in matrix polymerization and a transmembrane domain from which the ectodomain must be released. Using confocal microscopy an...
متن کاملIntactness of zona pellucida does not affect the secretion of a trypsin-like protease from mouse blastocyst.
Assisted hatching (AH), which is known to improve the hatching potential of mammalian embryos, has been used to increase the pregnancy rate in in vitro fertilization cycles. However, the effect of AH on a trypsin-like protease, which is known to be associated with the hatching process, has not been studied. In this study, we evaluate whether the intactness of zona pellucida affects the secretio...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 4 شماره
صفحات -
تاریخ انتشار 2015