1. Nat. Rev. Nephrol. doi:10.1038/nrneph.2017.101
Figure 5 Pathophysiology of autosomal dominant tubulointerstitial kidney disease (ADTKD)-UMOD
Figure 5 | Pathophysiology of autosomal dominant tubulointerstitial kidney disease (ADTKD)-UMOD. a | In physiological conditions, uromodulin is synthesized in the cells lining the thick ascending limb (TAL). The protein enters the secretory pathway and is directed to the apical membrane. Cleavage mediated by hepsin44 activates the uromodulin polymerization Zona Pellucida domain, enabling the formation of extracellular protein filaments. b | Mutations in UMOD that are associated with ADTKD cause endoplasmic reticulum (ER) retention and aggregation of mutant uromodulin. Mutant uromodulin that escapes ER quality control mechanisms reaches the apical membrane where it forms extracellular aggregates, rather than organized polymers. c | Immunofluorescence images showing extracellular uromodulin secreted by Madin–Darby canine kidney cells that stably express wild type (wt) or mutant (C317Y) uromodulin isoforms. d | Immunofluorescence images showing the localization of uromodulin in the TAL segments of 12 week-old transgenic mice expressing wt (TgUmodwt) or mutant (TgUmodC147W) uromodulin. Colocalization with calnexin (CNX) indicates ER accumulation of uromodulin in the mutant mice. e | Transmission electron microscopic image of kidneys from 24-week-old TgUmodC147W mice showing hyperplasia of ER membranes in a TAL cell.
Devuyst, O. et al. (2017) Uromodulin: from physiology to rare and complex kidney disorders
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