Divergent roles of rudhira in maintenance of filtration barrier integrity and function in drosophila nephrocytes and mouse kidney podocytes

Abstract

This thesis elucidates the molecular and cellular functions of Rudhira in regulating kidney function using Drosophila and mouse models. Drosophila nephrocytes are the structural and functional homolog of the mammalian kidney podocytes. This thesis characterizes the nephrocyte architecture in detail and reports that a unique cluster of actin filaments, maintained by multiple cellular components, is essential for filtration function. Further, it reports that the nephrocyte-specific protein Rudhira resides predominantly in the endoplasmic reticulum, regulates actin organization and is required for maintaining the ultrastructure and function. The added relevance of this nephrocyte study is demonstrated by analysis of Rudhira in the mouse kidney. We show that Rudhira is expressed in kidney podocytes. Podocyte-specific rudhira knockout mice have a disrupted podocyte filtration barrier with partial foot process effacement. This causes proteinuria, which is aggravated by toxin stress. Interestingly, toxin stress in wild type mice leads to increased Rudhira expression. Human Rudhira/BCAS3 was recently implicated in chronic kidney diseases. This thesis is the first report on the conserved role of Rudhira in nephrocyte/podocyte function, and provides valuable novel in vivo models for understanding chronic kidney diseases.