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Apolipoprotein L-1 renal risk variants form active channels at the plasma membrane driving cytotoxicity

Authors :
Joseph A Giovinazzo
Russell P Thomson
Nailya Khalizova
Patrick J Zager
Nirav Malani
Enrique Rodriguez-Boulan
Jayne Raper
Ryan Schreiner
Source :
eLife, Vol 9 (2020)
Publication Year :
2020
Publisher :
eLife Sciences Publications Ltd, 2020.

Abstract

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.

Details

Language :
English
ISSN :
2050084X
Volume :
9
Database :
Directory of Open Access Journals
Journal :
eLife
Publication Type :
Academic Journal
Accession number :
edsdoj.1efab0b621c4423f824ff25de7c99d4e
Document Type :
article
Full Text :
https://doi.org/10.7554/eLife.51185