Recruitment of APOL1 kidney disease risk variants to lipid droplets attenuates cell toxicity
Abstract
Specific APOL1 variants are a strong risk factor for human kidney disease. Previous reports examining the intracellular localization of the APOL1 protein in kidney and glomerular podocytes have yielded inconsistent results. Here we demonstrate differential localization of wild-type and risk variant APOL1 polypeptides, with the wild type localizing predominantly to lipid droplets and risk variant forms localizing predominantly to the endoplasmic reticulum. We further demonstrate that the localization of risk variant APOL1 modulates cytotoxic effects, and that perturbations increasing lipid droplet localization of risk variant polypeptides decrease this cytotoxicity. These findings have significant implications for understanding the disease mechanism of APOL1-associated kidney disease and for development of new therapeutic approaches.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Feb 07, 2019
- Source ID
- 10.1073/pnas.1820414116
Entities
People
- Balajikarthick Subramanian
- Cristian Riella
- David J. Friedman
- Jia-yue Zhang
- Jose M. Magraner
- Justin Chun
- Maris S. Wilkins
- Martin R. Pollak
- Seth L. Alper
Organizations
- Alberta Innovates – Health Solutions
- Ellison Medical Foundation
- Harvard Medical School
- National Institute of Diabetes and Digestive and Kidney Diseases
- Nephcure Foundation
- United States Department of Defense
- University of Calgary
- Vertex Pharmaceuticals