Human trypanolytic factor APOL1 forms pH-gated cation-selective channels in planar lipid bilayers: Relevance to trypanosome lysis

Significance African trypanosomes are parasites that can cause African sleeping sickness in humans. Host defense against some of these is provided by the human serum factor apolipoprotein L-1 (APOL1), which causes swelling and lysis of susceptible trypanosomes. Lysis follows uptake of APOL1 into acidic parasite endosomes and is thought to involve ion influx across the plasma membrane. In this paper we show that, after interaction of APOL1 with lipid bilayers at acidic pH, subsequent pH neutralization triggers the opening of pH-gated channels that selectively conduct cations across the bilayer. Based on these results, we propose a mechanism of trypanosome lysis that involves endocytic recycling of APOL1 and the opening of APOL1-induced cation-selective channels, at neutral pH, in the parasite plasma membrane.