Physiology Commons^™

Lrrk2 Deficiency Impairs Trans-Golgi To Lysosome Trafficking And Endocytic Cargo Degradation In Human Renal Proximal Tubule Epithelial Cells, Nathan J. Lanning, Calvin Vanopstall, Megan L. Goodall, Jeffrey P. Mackeigan

University Faculty Publications and Creative Works

Defects in vesicular trafficking underlie a wide variety of human diseases. Genetic disruption of leucine-rich repeat kinase 2 (LRRK2) in rodents results in epithelial vesicular trafficking errors that can also be induced by treatment of animals with LRRK2 kinase inhibitors. Here we demonstrate that defects in human renal cells lacking LRRK2 phenocopy those seen in the kidneys of Lrrk2 knockout mice, characterized by accumulation of intracellular waste vesicles and fragmentation of the Golgi apparatus. This phenotype can be recapitulated by knockdown of N-ethylmaleimide-sensitive factor, which physically associates with LRRK2 in renal cells. Deficiency in either protein leads to a defect …