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Published ahead of print on February 25, 2009
J Am Soc Nephrol 20: 473-478, 2009
© 2009 American Society of Nephrology
doi: 10.1681/ASN.2008070694
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Brief Review

Lipid–Protein Interactions along the Slit Diaphragm of Podocytes

Bernhard Schermer* and Thomas Benzing*,{dagger}

* Department of Medicine and Centre for Molecular Medicine and {dagger} Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany

Correspondence: Dr. Thomas Benzing, Renal Division, Department of Medicine, University of Cologne, Kerpener Strasse 62, 50937 Cologne, Germany. Phone: +49-221-478-4480; Fax: +49-221-478-5959; E-mail: thomas.benzing{at}uk-koeln.de

Podocytes are visceral epithelial cells supporting the function of the glomerular filter. Interdigitating foot processes of podocytes enwrap the glomerular capillaries and are connected by a highly specialized cell junction, the slit diaphragm. Signal transduction at the slit diaphragm is essential for the proper function of the kidney filtration barrier. The slit diaphragm constitutes a dynamic multiprotein signaling complex that contains structural proteins, receptors, signaling adaptors, ion channels, and scaffolding proteins. Function of some of these proteins requires cholesterol attached to the multiprotein complex. Recruitment of cholesterol is achieved through the PHB domain protein podocin, a member of a novel family of lipid-binding proteins that are conserved through evolution. The finding that cholesterol interaction regulates the activity of ion channels at the glomerular filtration barrier has important implications for renal physiology and pathophysiology.




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