%0 Journal Article
%T Rho-GTPase Signalling in the Pathogenesis of Nephrotic Syndrome
%A Richard Robins
%A Tomoko Takano
%J Advances in Nephrology
%D 2014
%R 10.1155/2014/903158
%X 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-GDI¦Á. 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. 1. Introduction The kidneys perform a number of essential functions in vertebrates including hormone secretion [1], blood pressure regulation [2], maintenance of glucose homeostasis [3], and urine formation. The latter process begins at the level of the glomerulus, the most proximal portion of the nephron, the kidney¡¯s functional unit [4]. Reports estimate the number of nephrons per kidney as one million [4, 5]. Our perception of the glomerulus has evolved over time from that of a static structure to a highly dynamic signalling hub that is capable of integrating intracellular cues from its individual structural components [4]. In humans, kidney development begins at five weeks gestation and the full complement of glomeruli is attained by 34 weeks [6]. Individual glomeruli begin development in utero following reciprocal interactions between the ureteric bud and metanephric mesenchyme. Mesenchymal cells are induced to coalesce and undergo a mesenchymal to epithelial transition into structures known as renal vesicles. The renal vesicles undergo a series of morphologic changes, maturing in developmental order to the comma-shape body, S-shape body, precapillary invasion stage, and finally the mature glomerulus [4, 7, 8]. Importantly, the
%U http://www.hindawi.com/journals/an/2014/903158/