Abstract: TH-PO1067
The Drosophila Nephrocyte Model of Podocyte Slit Diaphragms Reveals a Role for the Basal Polarity Complex in Slit Diaphragm Formation
Session Information
- Glomerular Diseases: Podocyte Biology - I
November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1204 Podocyte Biology
Author
- Poulton, John S., University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
Background
The podocyte slit diaphragm (SD) plays a key role in glomerular filtration. Mutations in the apical polarity protein Crb2 are present in some cases of steroid-resistant nephrotic syndrome. Animal models indicate an important role for apical polarity proteins in podocyte polarity and SD formation, suggesting cell polarity is a central aspect of podocyte development and function. Surprisingly however, mutations in basal polarity proteins do not cause significant defects in mouse podocytes, even though they express basal polarity proteins. Thus, it is difficult to interpret the relationships between the polarity complexes in podocyte development and SD formation.
Methods
To explore the potential role of the basal polarity proteins in SD formation, I performed a genetic analysis of the basal polarity proteins in SD formation and SD protein localization using the Drosophila nephrocyte, a popular model for podocyte SDs.
Results
I found that all of the canonical basal polarity proteins (Dlg, Scrib, Lgl, and Par-1) play important roles in the localization of nephrocyte SD proteins (Nephrin, Neph1, ZO-1). Loss of Dlg was also associated with dramatically reduced nephrocyte SD number and SD mislocalization; I am currently examining the role of the other basal proteins on SD formation. Loss of Dlg also appears to perturb Crb localization, suggesting the basal and apical polarity complexes function together in nephrocyte SD formation. Importantly, genetic interaction studies suggest the basal proteins work in concert to direct the formation of the nephrocyte SD. Genetic interaction studies also identified an important relationship between the basal polarity proteins and the SD-associated polarity protein Par-3, as well as the SD adaptor protein ZO-1.
Conclusion
Genetic analysis of the Drosophila nephrocyte has revealed a key role of the basal polarity proteins in SD formation. The genetic interaction studies are consistent with these proteins working as a conserved module, determining the localization of core SD components, likely through their interactions with proteins such as Par-3 and ZO-1. We are continuing to define the mechanism by which the basal polarity complex contributes to SD formation, their relationship with apical polarity proteins like Crb, and extending our analysis of the basal polarity proteins to a vertebrate podocyte model.