Evidence map›Paper›PMID 33975644›Full record

ArticleCell & bioscience2021

Slit diaphragm maintenance requires dynamic clathrin-mediated endocytosis facilitated by AP-2, Lap, Aux and Hsc70-4 in nephrocytes.

Luyao Wang, Pei Wen, Joyce van de Leemput, Zhanzheng Zhao, Zhe Han

Open access · goldAbstract read
In one paragraph

Article in Cell & bioscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
3.9field-weighted citation impact, top 6% 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

18 citing papers in PubMed, 33 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Piezo, Nephrocyte Function, and Slit Diaphragm Maintenance in Drosophila.Journal of the American Society of Nephrology : JASN · 2025
    Article
  8. Review
  9. Article
  10. AbioRxiv : the preprint server for biology · 2024
    Article
  11. Article
  12. Article
  13. Insights into human kidney function from the study of Drosophila.Pediatric nephrology (Berlin, Germany) · 2023
    Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. UsingFrontiers in cell and developmental biology · 2022
    Review
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

5 authors at 2 institutions in 2 countries.

Luyao Wang *Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe Eastern Road, Zhengzhou, 450052, Henan, China.
Pei Wen *Center for Precision Disease Modeling, Department of Medicine, University of Maryland School of Medicine, 670 West Baltimore Street, Baltimore, MD, 21201, USA.
Joyce van de LeemputCenter for Precision Disease Modeling, Department of Medicine, University of Maryland School of Medicine, 670 West Baltimore Street, Baltimore, MD, 21201, USA.
Zhanzheng ZhaoDepartment of Nephrology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe Eastern Road, Zhengzhou, 450052, Henan, China. zhanzhengzhao@zzu.edu.cn.
Zhe HanCenter for Precision Disease Modeling, Department of Medicine, University of Maryland School of Medicine, 670 West Baltimore Street, Baltimore, MD, 21201, USA. zhan@som.umaryland.edu.ORCID http://orcid.org/0000-0002-5177-7798
University of Maryland, Baltimore · USFirst Affiliated Hospital of Zhengzhou University · CN

Funding

Modeling Nephrotic Syndrome in Drosophila NephrocytesR01DK098410 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI HAN, ZHE · 2014 to 2022
$3.3M
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 DK098410NIDDK NIH HHS R01-DK098410NIDDK NIH HHS R01 DK120908NIDDK NIH HHS R01-DK120908
6 · The paper itself

Abstract

backgroundThe Slit diaphragm (SD) is the key filtration structure in human glomerular kidney that is affected in many types of renal diseases. SD proteins are known to undergo endocytosis and recycling to maintain the integrity of the filtration structure. However, the key components of this pathway remain unclear.

methodsUsing the Drosophila nephrocyte as a genetic screen platform, we screened most genes involved in endocytosis and cell trafficking, and identified the key components of the cell trafficking pathway required for SD protein endocytosis and recycling.

resultsWe discovered that the SD protein endocytosis and recycling pathway contains clathrin, dynamin, AP-2 complex, like-AP180 (Lap), auxilin and Hsc70-4 (the endocytosis part) followed by Rab11 and the exocyst complex (the recycling part). Disrupting any component in this pathway led to disrupted SD on the cell surface and intracellular accumulation of mislocalized SD proteins. We also showed the first in vivo evidence of trapped SD proteins in clathrin-coated pits at the plasma membrane when this pathway is disrupted.

conclusionsAll genes in this SD protein endocytosis and recycling pathway, as well as SD proteins themselves, are highly conserved from flies to humans. Thus, our results suggest that the SD proteins in human kidney undergo the same endocytosis and recycling pathway to maintain the filtration structure, and mutations in any genes in this pathway could lead to abnormal SD and renal diseases.

Indexed as

AP-2 complexAuxilinClathrinDrosophilaEndocytosisHsc70-4LapNephrocyteShiSlit diaphragm

Identifiers

PMID33975644
PMCPMC8111712
OpenAlexW3161393970

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.