Recently evolved alleles of Apolipoprotein L-1 (APOL1) provide increased protection against African trypanosome parasites while also significantly increasing the risk of developing kidney disease in humans. APOL1 protects against trypanosome infections by forming ion channels within the parasite, causing lysis. While the correlation to kidney disease is robust, there is little consensus concerning the underlying disease mechanism. We show in human cells that the APOL1 renal risk variants have a population of active channels at the plasma membrane, which results in an influx of both Na+ and Ca2+. We propose a model wherein APOL1 channel activity is the upstream event causing cell death, and that the activate-state, plasma membrane-localized channel represents the ideal drug target to combat APOL1-mediated kidney disease.
- Enrique Javier Rodriguez-Boulan
- Jayne Raper
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Christine Clayton, DKFZ-ZMBH Alliance, Germany
- Received: August 19, 2019
- Accepted: May 14, 2020
- Accepted Manuscript published: May 19, 2020 (version 1)
© 2020, Giovinazzo et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.