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

The 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 un...

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Bibliographic Details
Published in:Cell & bioscience 2021-05, Vol.11 (1), p.83-83, Article 83
Main Authors: Wang, Luyao, Wen, Pei, van de Leemput, Joyce, Zhao, Zhanzheng, Han, Zhe
Format: Article
Language:English
Subjects:
Cell surface
Clathrin
Coated pits
Cytoskeleton
Drosophila
Dynamin
Endocytosis
Filtration
Genetic aspects
Genetic screening
Genotype & phenotype
Heat shock proteins
Hsc70 protein
Insects
Kidney diseases
Kidneys
Kinases
Localization
Mammals
Mutation
Nephrocyte
Protein turnover
Proteins
Shi
Slit diaphragm
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Summary:The 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. Using 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. We 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. All 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.
ISSN:2045-3701
2045-3701
DOI:10.1186/s13578-021-00595-4