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.
