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• W3142119572 abstract "Significance Statement Apical polarity proteins are key regulators of podocyte function, particularly with respect to slit diaphragm (SD) integrity. However, no experimental evidence demonstrates basolateral polarity proteins regulate SDs, suggesting apicobasal polarity in itself may not be important. Using Drosophila nephrocyte SDs as a model, this study reports the basolateral polarity module promotes SD integrity through roles in endocytic trafficking. These findings suggest apicobasal polarity proteins are cooperative regulators of SDs, and connect these polarity proteins to other pathways important for SD integrity. Background Podocyte slit diaphragms (SDs) are intercellular junctions that function as size-selective filters, excluding most proteins from urine. Abnormalities in SDs cause proteinuria and nephrotic syndrome. Podocytes exhibit apicobasal polarity, which can affect fundamental aspects of cell biology, including morphology, intercellular junction formation, and asymmetric protein distribution along the plasma membrane. Apical polarity protein mutations cause nephrotic syndrome, and data suggest apical polarity proteins regulate SD formation. However, there is no evidence that basolateral polarity proteins regulate SDs. Thus, the role of apicobasal polarity in podocytes remains unclear. Methods Genetic manipulations and transgenic reporters determined the effects of disrupting apicobasal polarity proteins in Drosophila nephrocytes, which have SDs similar to those of mammalian podocytes. Confocal and electron microscopy were used to characterize SD integrity after loss of basolateral polarity proteins, and genetic-interaction studies illuminated relationships among apicobasal polarity proteins. Results The study identified four novel regulators of nephrocyte SDs: Dlg, Lgl, Scrib, and Par-1. These proteins comprise the basolateral polarity module and its effector kinase. The data suggest these proteins work together, with apical polarity proteins, to regulate SDs by promoting normal endocytosis and trafficking of SD proteins. Conclusions Given the recognized importance of apical polarity proteins and SD protein trafficking in podocytopathies, the findings connecting basolateral polarity proteins to these processes significantly advance our understanding of SD regulation." @default.
• W3142119572 created "2021-04-13" @default.
• W3142119572 creator A5077356959 @default.
• W3142119572 creator A5079086627 @default.
• W3142119572 date "2021-06-01" @default.
• W3142119572 modified "2023-10-12" @default.
• W3142119572 title "The Basolateral Polarity Module Promotes Slit Diaphragm Formation in Drosophila Nephrocytes, a Model of Vertebrate Podocytes" @default.
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• W3142119572 doi "https://doi.org/10.1681/asn.2020071050" @default.
• W3142119572 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8259641" @default.
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