A proteomic investigation of glomerular podocytes from a Denys-Drash Syndrome patient with a mutation in the Wilms tumour suppressor gene WT1

Viney, R. L., Morrison, A. A., van den Heuvel, L. P., Ni, L., Mathieson, P. W., Saleem, M. A. and Ladomery, M. (2007) A proteomic investigation of glomerular podocytes from a Denys-Drash Syndrome patient with a mutation in the Wilms tumour suppressor gene WT1. Proteomics, 7 (5). pp. 804-815. ISSN 1615-9861

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Publisher's URL: http://dx.doi.org/10.1002/pmic.200600666

Abstract

Glomerular podocytes are essential for blood filtration in the kidney underpinned by their unique cytoskeletal morphology. An increasing number of kidney diseases are being associated with key podocyte abnormalities. The Wilms tumour suppressor gene (WT1) encodes a zinc finger protein with a crucial role in normal kidney development; and in the adult, WT1 is required for normal podocyte function. Denys-Drash Syndrome (DDS) results from mutations affecting the zinc finger domain of WT1. The aim of this study was to undertake, for the first time, a proteomic analysis of cultured human podocytes; and to analyse the molecular changes in DDS podocytes. The morphology of DDS podocytes was highly irregular, reminiscent of a fibroblastic appearance. A reference 2-D gel was generated, and 75 proteins were identified of which 43% involved in cytoskeletal architecture. The DDS and wild-type proteomes were compared by 2-D DIGE. The level of 95.6% of proteins was unaltered; but 4.4% were altered more than two-fold. A sample of proteins involved in cytoskeletal architecture appeared to be misexpressed in DDS podocytes. Consistent with this finding, overall levels of filamentous actin also appeared reduced in DDS podocytes. We conclude that one of WT1 functions in podocytes is to regulate the expression of key components and regulators of the cytoskeleton.

Item Type:Article
Uncontrolled Keywords:2-D DIGE, cytoskeletal architecture, Denys-Drash Syndrome, podocytes, WT1
Faculty/Department:Faculty of Environment and Technology
Faculty of Health and Applied Sciences > Department of Biological, Biomedical and Analytical Sciences
ID Code:5787
Deposited By: R. Upload account
Deposited On:22 Jan 2010 15:10
Last Modified:22 Aug 2013 14:51

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