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Cell Biological and Biochemical Characterization of Drebrin Complexes in Mesangial Cells and Podocytes of Renal Glomeruli

Wiebke K. Peitsch^*, Ilse Hofmann^*, Nicole Endlich, Silke Prätzel^*, Cäcilia Kuhn^*, Herbert Spring, Hermann-Josef Gröne^¶, Wilhelm Kriz and Werner W. Franke^*

*Division of Cell Biology, German Cancer Research Center, Heidelberg, Germany; Department of Dermatology, Venerology and Allergology, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany; Department of Anatomy and Cell Biology I, University of Heidelberg, Heidelberg, Germany; Biomedical Structure Analysis Group, German Cancer Research Center, Heidelberg, Germany; and ^¶Division of Cellular und Molecular Pathology, German Cancer Research Center, Heidelberg, Germany.

Correspondence to Dr. Werner W. Franke, Divison of Cell Biology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. Phone: 49-6221-423213; Fax: 49-6221-423404;

ABSTRACT. Drebrins are actin-binding proteins (ABP) initially identified in and thought to be specific for neuronal cells, where they appear to contribute to the formation of cell processes. Recent studies have also detected the isoform drebrin E2 in a wide range of non-neuronal cell types, notably in and near actin-rich lamellipodia and filopodia. The present study demonstrates drebrin enrichment in renal glomeruli. Immunohistochemistry and double-label confocal laser scanning microscopy have shown intense drebrin reactions in the mesangial cells of diverse mammalian species. In adult human and bovine kidneys, drebrin is, in addition, markedly enriched in the foot processes of podocytes, as also demonstrable by immunoelectron microscopy. By contrast, the podocytes of rodent glomeruli appear to contain significant drebrin concentrations only during early developmental stages. In differentiated murine podocytes cultured in vitro, however, drebrin is concentrated in the cell processes, where it partially codistributes with actin and other ABP. In biochemical analyses using protein extracts from renal cortices, large (approximately 20S) complexes ("drebrosomes") were found containing drebrin and actin. These findings confirm and extend our hypothesis that drebrin is involved in the regulation of actin dynamics also outside the nervous system. Clearly, drebrin has to be added to the ensemble of ABP regulating the actomyosin system and the dynamics of mesangial cells and foot processes in podocytes. E-mail: w.franke@dkfz.de

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Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673