Uromodulin trafficking rescued in kidney disease
Uromodulin (UMOD) is the most abundant protein in human urine, is mutated in autosomal dominant tubulointerstitial kidney disease (ADTKD-UMOD), causing an incurable genetic disorder leading to kidney failure.
Mutant UMOD is entrapped in kidney epithelial cells, but the precise trafficking disruption mechanisms is not clear.
The researchers demonstrate that transmembrane Emp24 protein transport domain–containing (TMED) cargo receptors TMED2, TMED9, and TMED10 bind UMOD and regulate its trafficking along the secretory pathway.
Targeting of TMEDs pharmacologically reduced intracellular accumulation of mutant UMOD and restored trafficking and localization of UMOD to the apical plasma membrane.
