Kidney Injury Molecule-1 Enhances Endocytosis of Albumin in Renal Proximal Tubular Cells.
Receptor-mediated endocytosis plays an important role in albumin reabsorption by renal proximal tubule epithelial cells. Kidney injury molecule-1 (KIM-1) is a scavenger receptor that is upregulated on the apical membrane of proximal tubules in proteinuric kidney disease. In this study, we examined the cellular localization and functional role of KIM-1 in cultured renal tubule epithelial cells (TECs). Confocal immunofluorescence microscopy reveals intracellular and cell surface localization of KIM-1 in primary renal TECs. Albumin stimulation resulted in a redistribution of KIM-1 and tight junction protein zonula occludens-1 in primary TEC monolayer. An increase in albumin internalization was observed in both primary TECs expressing endogenous KIM-1 and rat kidney cell line (NRK-52E) overexpressing exogenous KIM-1. KIM-1-induced albumin accumulation was abolished by its specific antibody. Moreover, endocytosed KIM-1 and its cargo proteins were delivered from endosomes to lysosomes for degradation in a clathrin-dependent pathway. Supportive evidence includes (1) detection of KIM-1 in Rab5-positive early endosomes, Rab7-positive late endosomes/multivesicular bodies, and LAMP1-positive lysosomes, (2) colocalization of KIM-1 and clathrin in the intracellular vesicles, and (3) blockade of KIM-1-mediated albumin internalization by chlorpromazine, an inhibitor of clathrin-dependent endocytosis. KIM-1 expression was upregulated by albumin but downregulated by transforming growth factor-β1. Taken together, our data indicate that KIM-1 increases albumin endocytosis in renal tubule epithelial cells, at least partially via a clathrin-dependent mechanism. J. Cell. Physiol. 231: 896-907, 2016. © 2015 Wiley Periodicals, Inc.
Department of Physiology, Morehouse School of Medicine, Atlanta, Georgia.
Xueying
X
Zhao
Department of Physiology, Morehouse School of Medicine, Atlanta, Georgia.
Chen
C
Jiang
Department of Physiology, Morehouse School of Medicine, Atlanta, Georgia.
Rebecca
R
Olufade
Department of Physiology, Morehouse School of Medicine, Atlanta, Georgia.
Dong
D
Liu
Department of Physiology, Morehouse School of Medicine, Atlanta, Georgia.
Nerimiah
N
Emmett
D000818:Animals; D002450:Cell Communication; D002451:Cell Compartmentation; D002478:Cells, Cultured; D002966:Clathrin / Q000378:metabolism; D004705:Endocytosis; D004847:Epithelial Cells / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives* / Q000378:metabolism; D000072596:Hepatitis A Virus Cellular Receptor 1 / Q000378:metabolism*; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000166:cytology* / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D051381:Rats; D012710:Serum Albumin, Bovine / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D002966:Clathrin; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D053773:Transforming Growth Factor beta1; C039217:fluorescein isothiocyanate bovine serum albumin; D012710:Serum Albumin, Bovine; D016650:Fluorescein-5-isothiocyanate