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http://purl.uniprot.org/citations/33975644http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/33975644http://www.w3.org/2000/01/rdf-schema#comment"

Background

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.

Methods

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.

Results

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.

Conclusions

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."xsd:string
http://purl.uniprot.org/citations/33975644http://purl.org/dc/terms/identifier"doi:10.1186/s13578-021-00595-4"xsd:string
http://purl.uniprot.org/citations/33975644http://purl.uniprot.org/core/author"Wang L."xsd:string
http://purl.uniprot.org/citations/33975644http://purl.uniprot.org/core/author"Zhao Z."xsd:string
http://purl.uniprot.org/citations/33975644http://purl.uniprot.org/core/author"Han Z."xsd:string
http://purl.uniprot.org/citations/33975644http://purl.uniprot.org/core/author"Wen P."xsd:string
http://purl.uniprot.org/citations/33975644http://purl.uniprot.org/core/author"van de Leemput J."xsd:string
http://purl.uniprot.org/citations/33975644http://purl.uniprot.org/core/date"2021"xsd:gYear
http://purl.uniprot.org/citations/33975644http://purl.uniprot.org/core/name"Cell Biosci"xsd:string
http://purl.uniprot.org/citations/33975644http://purl.uniprot.org/core/pages"83"xsd:string
http://purl.uniprot.org/citations/33975644http://purl.uniprot.org/core/title"Slit diaphragm maintenance requires dynamic clathrin-mediated endocytosis facilitated by AP-2, Lap, Aux and Hsc70-4 in nephrocytes."xsd:string
http://purl.uniprot.org/citations/33975644http://purl.uniprot.org/core/volume"11"xsd:string
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