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JHC exPRESS: First Published June 13, 2005. doi:10.1369/jhc.4A6596.2005
Copyright © Histochemical Society, Inc.

A more recent version of this article appeared on November 1, 2005.
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Localization of {alpha}-Dystroglycan on the Podocyte: from Top to Toe

Nils P.J. Vogtländer 1, Henry Dijkman 1, Marinka A.H. Bakker 1, Kevin P. Campbell 1, Johan van der Vlag 1 and Jo H.M. Berden 1*

1 Division of Nephrology (NPJV,MAHB,JvdV,JHMB.) and Department of Pathology (HD), Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands, and the Department of Physiology and Biophysics (KPC), Howard Hughes Medical Institute, University of Iowa, Iowa City, Iowa

* To whom correspondence should be addressed. E-mail: j.berden{at}nier.umcn.nl.

Submitted on December 10, 2004
Accepted on 4 May 2005


  Abstract
{alpha}-Dystroglycan is a negatively charged membrane associated glycoprotein, which links the cytoskeleton to the extracellular matrix. Previously, we described that {alpha}-dystroglycan covers the whole podocyte cell membrane in the rat. However, our finding was challenged by the description of a strictly basolateral localization in human kidney biopsies, using a different antibody against {alpha}-dystroglycan. Therefore, we studied the exact localization of glomerular {alpha}-dystroglycan by using these two antibodies in both species. The studies were performed by using monoclonal antibodies IIH6 and VIA4.1 in immunofluorescence, confocal microscopy and immuno-electron microscopy on both rat and human kidney sections, as well as on cultured mouse podocytes. The apical localization of {alpha}-dystroglycan on podocytes was more dominant than the basolateral localization. The basolateral staining with MoAb VIA4.1 was more pronounced than that of MoAb IIH6. With both MoAb’s the staining in rat kidneys was more prominent in comparison to human kidneys. We conclude that {alpha}-dystroglycan is expressed at both the basolateral and apical side of the podocyte. This localization suggests that {alpha}-dystroglycan plays a dual role in the maintenance of the unique architecture of podocytes by its binding to the glomerular basement membrane, and in the maintenance of the integrity of the filtration slit, respectively.

Key Words: dystroglycan, podocyte, agrin, laminin, glomerulus, kidney, podocalyxin, renal


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