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KIBRA Modulates Directional Migration of Podocytes

Kerstin Duning^*, Eva-Maria Schurek^*,, Marc Schlüter^*, Michael Bayer^*, Hans-Christian Reinhardt^*, Albrecht Schwab, Liliana Schaefer, Thomas Benzing, Bernhard Schermer, Moin A. Saleem^||, Tobias B. Huber^¶, Sebastian Bachmann^**, Joachim Kremerskothen^*, Thomas Weide^* and Hermann Pavenstädt^*

^* Medizinische Klinik und Poliklinik D and Institut für Physiologie II, Universitätsklinikum Münster, Münster, Universitätsklinikum Frankfurt, Pharmazentrum, Frankfurt/Main, Universitätsklinikum Köln, Innere Medizin IV, Nephrologie und Allgemeine Innere Medizin, Köln, ^¶ Medizinische Universitätsklinik, Abteilung Innere Medizin IV, Freiburg, and ^** Charité–Universitätsmedizin Berlin, Institut für Vegetative Anatomie, Berlin, Germany; and ^|| Academic and Children's Renal Unit, University of Bristol, Bristol, United Kingdom

Correspondence: Dr. Thomas Weide, UKM, Medizinische Klinik und Poliklinik D, Abteilung: Molekulare Nephrologie, Domagkstrasse 3a, D-48149 Münster, Germany. Phone: +49-251-83-57939; Fax: +49-251-83-57943; E-mail: weidet{at}uni-muenster.de; or Prof. Hermann Pavenstädt, UKM, Medizinische Klinik und Poliklinik D, Albert-Schweizer Strasse 33, D-48149 Münster, Germany. Phone: +49-251-83-47516; Fax: +49-251-83-46979; E-mail: pavensth{at}mednet.uni-muenster.de

Received for publication August 20, 2007. Accepted for publication April 11, 2008.

Asymmetric delivery and distribution of macromolecules are essential for cell polarity and for cellular functions such as differentiation, division, and signaling. Injury of podocytes, which are polarized epithelial cells, changes the dynamics of the actin meshwork, resulting in foot process retraction and proteinuria. Although the spatiotemporal control of specific protein–protein interactions is crucial for the establishment of cell polarity, the mechanisms controlling polarity-dependent differentiation and division are incompletely understood. In this study, yeast two-hybrid screens were performed using a podocyte cDNA library and the polarity protein PATJ as bait. The protein KIBRA was identified as an interaction partner of PATJ and was localized to podocytes, tubular structures, and collecting ducts. The last four amino acids of KIBRA mediated binding to the eighth PDZ domain of PATJ. In addition, KIBRA directly bound to synaptopodin, an essential organizer of the podocyte cytoskeleton. Stable knockdown of KIBRA in immortalized podocytes impaired directed cell migration, suggesting that KIBRA modulates the motility of podocytes by linking polarity proteins and cytoskeleton-associated protein complexes.

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