ArticleProceedings of the National Academy of Sciences of the United States of America2015
Human trypanolytic factor APOL1 forms pH-gated cation-selective channels in planar lipid bilayers: relevance to trypanosome lysis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 127 citations in OpenAlex.
- Nutritional markers and proteome in patients undergoing treatment for pulmonary tuberculosis differ by geographic region.PloS one · 2021Trial
- APOL1 kidney disease: a critical narrative review of molecular mechanisms, clinical heterogeneity, and the emerging therapeutic landscape.International urology and nephrology · 2026Review
- Germline-targeted baboon apolipoprotein L-1 protects mice against African trypanosomes.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- APOL1 plasma membrane pools resist rapid protein degradation.Scientific reports · 2026Article
- APOL1-mediated kidney disease: a narrative review of the lessons learnt from the past 15 years.BMC nephrology · 2025Review
- A novelRenal failure · 2025Article
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- Small molecule APOL1 inhibitors as a precision medicine approach for APOL1-mediated kidney disease.Nature communications · 2025Article
- Advances in kidney disease: pathogenesis and therapeutic targets.Frontiers in medicine · 2025Review
- Review
- Differing sensitivities to angiotensin converting enzyme inhibition of kidney disease mediated by APOL1 high-risk variants G1 and G2.Kidney international · 2024Article
- Review
- Identifying microRNAs Possibly Implicated in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia: A Review.International journal of molecular sciences · 2024Review
- APOL1 polymorphisms are not influencing acute coronary syndrome risk in Czech males.Molecular genetics & genomic medicine · 2024Article
- The Janus-faced functions of Apolipoproteins L in membrane dynamics.Cellular and molecular life sciences : CMLS · 2024Article
- Phenome-wide analysis reveals epistatic associations between APOL1 variants and chronic kidney disease and multiple other disorders.EBioMedicine · 2024Article
- APOL1-mediated monovalent cation transport contributes to APOL1-mediated podocytopathy in kidney disease.The Journal of clinical investigation · 2024Article
22 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
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Abstract
Apolipoprotein L-1 (APOL1), the trypanolytic factor of human serum, can lyse several African trypanosome species including Trypanosoma brucei brucei, but not the human-infective pathogens T. brucei rhodesiense and T. brucei gambiense, which are resistant to lysis by human serum. Lysis follows the uptake of APOL1 into acidic endosomes and is apparently caused by colloid-osmotic swelling due to an increased ion permeability of the plasma membrane. Here we demonstrate that nanogram quantities of full-length recombinant APOL1 induce ideally cation-selective macroscopic conductances in planar lipid bilayers. The conductances were highly sensitive to pH: their induction required acidic pH (pH 5.3), but their magnitude could be increased 3,000-fold upon alkalinization of the milieu (pK(a) = 7.1). We show that this phenomenon can be attributed to the association of APOL1 with the bilayer at acidic pH, followed by the opening of APOL1-induced cation-selective channels upon pH neutralization. Furthermore, the conductance increase at neutral pH (but not membrane association at acidic pH) was prevented by the interaction of APOL1 with the serum resistance-associated protein, which is produced by T. brucei rhodesiense and prevents trypanosome lysis by APOL1. These data are consistent with a model of lysis that involves endocytic recycling of APOL1 and the formation of cation-selective channels, at neutral pH, in the parasite plasma membrane.
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