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NDT Advance Access originally published online on June 5, 2007
Nephrology Dialysis Transplantation 2007 22(8):2124-2128; doi:10.1093/ndt/gfm344
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© The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Molecular architecture of the glomerular slit diaphragm: lessons learnt for a better understanding of disease pathogenesis

Harry Holthöfer

National Center of Sensor Research/BioAnalytical Sciences, Dublin City University, Ireland

Correspondence and offprint requests to: Harry Holthöfer, MD, PhD, Biomedicum Helsinki, University of Helsinki, PB 63, FI-00014, Finland. Email: harry.holthofer@helsinki.fi

Keywords: cell-adhesion molecules; intercellular junctions; proteinuria; podocyte

The first 150 words of the full text of this article appear below.



   Introduction
 
For more than three decades, the molecular composition of the interpodocyte slit diaphragm of the glomerular filtration barrier has remained elusive. The first electron microscopic studies described the slit diaphragm as a porous, ‘zipper-like’ structure [1], but it was not until 1998 that the first transmembrane molecule of the slit diaphragm was identified [2]: Nephrin is a cell surface receptor of the immunoglobulin superfamily participating in cell–cell adhesion and signalling functions [3]. Mutations in nephrin lead to the congenital nephrotic syndrome of the Finnish type (CNF), suggesting that nephrin is of pivotal importance for maintaining the filtration barrier. In recent years, the mapping of the genetic background of other inherited and acquired nephropathies and the generation of transgenic animal models have led to the beginning of a new era in nephrology, also promising new targeted therapies and advanced diagnostics. In the present review, the . . . [Full Text of this Article]



   The slit diaphragm of the glomerular capillary wall
 


   Nephrin forms the scaffold for intertwining slit molecules
 


   Signalling at the slit diaphragm
 


   Nephrin-like proteins are essential for cell–cell adhesion at the slit diaphragm
 


   P-cadherin and FAT1 localize to the slit diaphragm
 


   Intracellular scaffold and adaptor proteins of podocytes
 


   Conclusion
 

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