Table of Contents
Advances in Nephrology
Volume 2014 (2014), Article ID 903158, 11 pages
http://dx.doi.org/10.1155/2014/903158
Review Article

Rho-GTPase Signalling in the Pathogenesis of Nephrotic Syndrome

Division of Nephrology, McGill University Health Centre, 3775 University Street, Room 236, Montreal, QC, Canada H3A 2B4

Received 2 March 2014; Accepted 21 May 2014; Published 15 June 2014

Academic Editor: James Stockand

Copyright © 2014 Richard Robins and Tomoko Takano. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Nephrotic syndrome (NS) is characterized by heavy proteinuria, hypoalbuminemia, and edema. The underlying causes of NS are diverse and are tied to inheritable and environmental factors. A common diagnostic marker for NS is effacement of podocyte foot processes. The formation and maintenance of foot processes are under the control of many signalling molecules including Rho-GTPases. Our knowledge of Rho-GTPases is based largely on the functions of three prototypic members: RhoA, Rac1, and Cdc42. In the event of podocyte injury, the rearrangement to the actin cytoskeleton is orchestrated largely by this family of proteins. The importance of maintaining proper actin dynamics in podocytes has led to much investigation as to how Rho-GTPases and their regulatory molecules form and maintain foot processes as a critical component of the kidney’s filtration barrier. Modern sequencing techniques have allowed for the identification of novel disease causing mutations in genes such as ARHGDIA, encoding Rho-GDIα. Continued use of whole exome sequencing has the potential to lead to the identification of new mutations in genes encoding Rho-GTPases or their regulatory proteins. Expanding our knowledge of the dynamic regulation of the actin network by Rho-GTPases in podocytes will pave the way for effective therapeutic options for NS patients.