ArticleJCI insight2017
APOL1 variants change C-terminal conformational dynamics and binding to SNARE protein VAMP8.
Article in JCI insight, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Genome-wide association study for time to failure of kidney transplants from African American deceased donors.Clinical transplantation · 2020Pooled it
- Molecular Mechanisms of APOL1-Associated Kidney Disease.International journal of molecular sciences · 2026Review
- Article
- APOL1-mediated kidney disease: a narrative review of the lessons learnt from the past 15 years.BMC nephrology · 2025Review
- Article
- Review
- The Janus-faced functions of Apolipoproteins L in membrane dynamics.Cellular and molecular life sciences : CMLS · 2024Article
- Apolipoprotein L1 (APOL1) renal risk variant-mediated podocyte cytotoxicity depends on African haplotype and surface expression.Scientific reports · 2024Article
- Apolipoproteins L1 and L3 control mitochondrial membrane dynamics.Cell reports · 2023Article
- A SNARE protective pool antagonizes APOL1 renal toxicity in Drosophila nephrocytes.Cell & bioscience · 2023Article
- Essential role of Wtip in mouse development and maintenance of the glomerular filtration barrier.American journal of physiology. Renal physiology · 2022Article
- Inhibition of endoplasmic reticulum stress signaling rescues cytotoxicity of human apolipoprotein-L1 risk variants in Drosophila.Kidney international · 2022Article
- DGAT2 Inhibition Potentiates Lipid Droplet Formation To Reduce Cytotoxicity in APOL1 Kidney Risk Variants.Journal of the American Society of Nephrology : JASN · 2022Article
- Variant APOL1 protein in plasma associates with larger particles in humans and mouse models of kidney injury.PloS one · 2022Article
- Evolution of Renal-Disease Factor APOL1 Results in Cis and Trans Orientations at the Endoplasmic Reticulum That Both Show Cytotoxic Effects.Molecular biology and evolution · 2021Article
- Structures of the ApoL1 and ApoL2 N-terminal domains reveal a non-classical four-helix bundle motif.Communications biology · 2021Article
- Apolipoprotein L1 and mechanisms of kidney disease susceptibility.Current opinion in nephrology and hypertension · 2021Review
- Podocyte density is reduced in kidney allografts with high-risk APOL1 genotypes at transplantation.Clinical transplantation · 2021Article
- Lack of APOL1 in proximal tubules of normal human kidneys and proteinuric APOL1 transgenic mouse kidneys.PloS one · 2021Article
- Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
APOL1 variants in African populations mediate resistance to trypanosomal infection but increase risk for kidney diseases through unknown mechanisms. APOL1 is expressed in glomerular podocytes and does not vary with underlying kidney disease diagnoses or APOL1 genotypes, suggesting that the kidney disease-associated variants dysregulate its function rather than its localization or abundance. Structural homology searches identified vesicle-associated membrane protein 8 (VAMP8) as an APOL1 protein interactor. VAMP8 colocalizes with APOL1 in the podocyte, and the APOL1:VAMP8 interaction was confirmed biochemically and with surface plasmon resonance. APOL1 variants attenuate this interaction. Computational modeling of APOL1's 3-dimensional structure, followed by molecular dynamics simulations, revealed increased motion of the C-terminal domain of reference APOL1 compared with either variant, suggesting that the variants stabilize a closed or autoinhibited state that diminishes protein interactions with VAMP8. Changes in ellipticity with increasing urea concentrations, as assessed by circular dichroism spectroscopy, showed higher conformational stability of the C-terminal helix of the variants compared with the reference protein. These results suggest that reference APOL1 interacts with VAMP8-coated vesicles, a process attenuated by variant-induced reduction in local dynamics of the C-terminal. Disordered vesicular trafficking in the podocyte may cause injury and progressive chronic kidney diseases in susceptible African Americans subjects.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.