Show simple item record

dc.contributor.authorWang, Luyao
dc.contributor.authorWen, Pei
dc.contributor.authorvan de Leemput, Joyce
dc.contributor.authorZhao, Zhanzheng
dc.contributor.authorHan, Zhe
dc.date.accessioned2021-05-14T13:36:27Z
dc.date.available2021-05-14T13:36:27Z
dc.date.issued2021-05-11
dc.identifier.urihttp://hdl.handle.net/10713/15650
dc.description.abstractBackground: 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.en_US
dc.description.urihttps://doi.org/10.1186/s13578-021-00595-4en_US
dc.language.isoenen_US
dc.publisherSpringer Natureen_US
dc.relation.ispartofCell & Bioscienceen_US
dc.subjectAP-2 complexen_US
dc.subjectAuxilinen_US
dc.subjectClathrinen_US
dc.subjectDrosophilaen_US
dc.subjectEndocytosisen_US
dc.subjectHsc70-4en_US
dc.subjectLapen_US
dc.subjectNephrocyteen_US
dc.subjectShien_US
dc.subjectSlit diaphragmen_US
dc.titleSlit diaphragm maintenance requires dynamic clathrin-mediated endocytosis facilitated by AP-2, Lap, Aux and Hsc70-4 in nephrocytesen_US
dc.typeArticleen_US
dc.identifier.doi10.1186/s13578-021-00595-4
dc.identifier.pmid33975644
dc.source.volume11
dc.source.issue1
dc.source.beginpage83
dc.source.endpage
dc.source.countryUnited States
dc.source.countryEngland


This item appears in the following Collection(s)

Show simple item record