Evidence map›Paper›PMID 37925499›Full record

ArticleCell & bioscience2023

A SNARE protective pool antagonizes APOL1 renal toxicity in Drosophila nephrocytes.

Jin-Gu Lee, Yulong Fu, Jun-Yi Zhu, Pei Wen, Joyce van de Leemput, Patricio E Ray, Zhe Han

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell & bioscience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.0field-weighted citation impact, top 24% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Article
  3. The Janus-faced functions of Apolipoproteins L in membrane dynamics.Cellular and molecular life sciences : CMLS · 2024
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Jin-Gu Lee *Center for Precision Disease Modeling, Department of Medicine, University of Maryland School of Medicine (UMSOM), 670 West Baltimore Street, 4052 HSFIII, Baltimore, MD, 21201, USA.ORCID http://orcid.org/0000-0001-9477-6990
Yulong Fu *Center for Precision Disease Modeling, Department of Medicine, University of Maryland School of Medicine (UMSOM), 670 West Baltimore Street, 4052 HSFIII, Baltimore, MD, 21201, USA.ORCID http://orcid.org/0000-0001-7991-9965
Jun-Yi Zhu *Center for Precision Disease Modeling, Department of Medicine, University of Maryland School of Medicine (UMSOM), 670 West Baltimore Street, 4052 HSFIII, Baltimore, MD, 21201, USA.ORCID http://orcid.org/0000-0002-4517-101X
Pei WenCenter for Precision Disease Modeling, Department of Medicine, University of Maryland School of Medicine (UMSOM), 670 West Baltimore Street, 4052 HSFIII, Baltimore, MD, 21201, USA.ORCID http://orcid.org/0000-0001-7065-6396
Joyce van de LeemputCenter for Precision Disease Modeling, Department of Medicine, University of Maryland School of Medicine (UMSOM), 670 West Baltimore Street, 4052 HSFIII, Baltimore, MD, 21201, USA.ORCID http://orcid.org/0000-0003-1903-7295
Patricio E RayChild Health Research Center, Department of Pediatrics, University of Virginia School of Medicine, 409 Lane Road, Charlottesville, VA, 22908, USA. Pray@virginia.edu.ORCID http://orcid.org/0000-0003-2223-9584
Zhe HanCenter for Precision Disease Modeling, Department of Medicine, University of Maryland School of Medicine (UMSOM), 670 West Baltimore Street, 4052 HSFIII, Baltimore, MD, 21201, USA. zhan@som.umaryland.edu.ORCID http://orcid.org/0000-0002-5177-7798
University of Maryland, Baltimore · USUniversity of Virginia Health System · US

Funding

Role of bFGF low affinity receptors in childhood HIVANR01DK049419 · NIDDK · UNIVERSITY OF VIRGINIA · PI PATRICIO E. RAY · 1994 to 2026
$7.4M
Modeling Nephrotic Syndrome in Drosophila NephrocytesR01DK098410 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI HAN, ZHE · 2014 to 2022
$3.3M
Role of cytokines and APOL-1 in the pathogenesis of childhood HIV associated nephrologyR01DK103564 · NIDDK · UNIVERSITY OF VIRGINIA · PI RAY, PATRICIO E. · 2014 to 2023
$3.0M
Novel mechanisms and Drosophila model of APOL1-HIV-1 nephropathies in childrenR01DK115968 · NIDDK · UNIVERSITY OF VIRGINIA · PI HAN, ZHE, RAY, PATRICIO E. · 2018 to 2022
$2.3M
Integrating Drosophila and human podocyte studies to discover APOL1 renal toxicity mechanism and therapeutic targetsR01DK120908 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI HAN, ZHE · 2019 to 2022
$1.4M
NIDDK NIH HHS R01 DK049419NIDDK NIH HHS R01 DK098410NIDDK NIH HHS R01DK098410NIDDK NIH HHS R01 DK103564NIDDK NIH HHS R01DK103564NIDDK NIH HHS R01DK115968NIDDK NIH HHS R01 DK120908NIDDK NIH HHS R01DK120908
6 · The paper itself

Abstract

backgroundPeople of Sub-Saharan African ancestry are at higher risk of developing chronic kidney disease (CKD), attributed to the Apolipoprotein L1 (APOL1) gene risk alleles (RA) G1 and G2. The underlying mechanisms by which the APOL1-RA precipitate CKD remain elusive, hindering the development of potential treatments.

resultsUsing a Drosophila genetic modifier screen, we found that SNARE proteins (Syx7, Ykt6, and Syb) play an important role in preventing APOL1 cytotoxicity. Reducing the expression of these SNARE proteins significantly increased APOL1 cytotoxicity in fly nephrocytes, the equivalent of mammalian podocytes, whereas overexpression of Syx7, Ykt6, or Syb attenuated their toxicity in nephrocytes. These SNARE proteins bound to APOL1-G0 with higher affinity than APOL1-G1/G2, and attenuated APOL1-G0 cytotoxicity to a greater extent than either APOL1-RA.

conclusionsUsing a Drosophila screen, we identified SNARE proteins (Syx7, Ykt6, and Syb) as antagonists of APOL1-induced cytotoxicity by directly binding APOL1. These data uncovered a new potential protective role for certain SNARE proteins in the pathogenesis of APOL1-CKD and provide novel therapeutic targets for APOL1-associated nephropathies.

Indexed as

APOL1NephrocytesRenal toxicitySerum resistance-associated (SRA) proteinSNARE protective poolSNARE proteins

Identifiers

PMID37925499
PMCPMC10625211
OpenAlexW4388347938

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.