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

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

eLife (2020-05-20)
Joseph A Giovinazzo, Russell P Thomson, Nailya Khalizova, Patrick J Zager, Nirav Malani, Enrique Rodriguez-Boulan, Jayne Raper, Ryan Schreiner
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.

MATERIALS
Product Number
Brand
Product Description

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Doxycycline hyclate
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Sodium pyruvate, powder, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥99%
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Fibronectin bovine plasma, solution, sterile-filtered, BioReagent, suitable for cell culture