Loss of podocyte apkcλ/ι causes polarity defects and nephrotic syndrome

Huber TB, Hartleben B, Winkelmann K, Schneider L, Becker JU, Leitges M, Walz G, Haller H, Schiffer M (2009)

Publication Type: Journal article

Publication year: 2009

Journal

Journal of the American Society of Nephrology American Society of Nephrology

Book Volume: 20

Pages Range: 798-806

Journal Issue: 4

DOI: 10.1681/ASN.2008080871

Abstract

Atypical protein kinase C (aPKC) is a central component of the evolutionarily conserved Par3-Par6- aPKC complex, one of the fundamental regulators of cell polarity. We recently demonstrated that these proteins interact with Neph-nephrin molecules at the slit diaphragm of the glomerular filtration barrier. Here, we report that podocyte-specific deletion of aPKCλ/ι in mice results in severe proteinuria, nephrotic syndrome, and death at 4 to 5 wk after birth. Podocyte foot processes of knockout mice developed structural defects, including mislocalization of the slit diaphragm. In the glomerulus, aPKCλ/ι was primarily expressed in developing glomerular epithelial cells and podocyte foot processes. Interestingly, under physiologic conditions, aPKCλ/ι translocated from the apical surface to the basolateral side of developing podocytes, and this translocation preceded the development of foot processes and formation of slit diaphragms. Supporting a critical role for aPKCλ/ι in the maintenance of slit diaphragms and podocyte foot processes, aPKCλ/ι associated with the Neph-nephrin slit diaphragm complex and localized to the tips of filopodia and leading edges of cultured podocytes. These results suggest that aPKC signaling is fundamental to glomer- ular maintenance and development. Copyright © 2009 by the American Society of Nephrology.

Authors with CRIS profile

Mario Schiffer

Involved external institutions

Medizinische Hochschule Hannover (MHH) / Hannover Medical School DE Germany (DE) Albert-Ludwigs-Universität Freiburg DE Germany (DE) University of Oslo NO Norway (NO)

How to cite

APA:

Huber, T.B., Hartleben, B., Winkelmann, K., Schneider, L., Becker, J.U., Leitges, M.,... Schiffer, M. (2009). Loss of podocyte apkcλ/ι causes polarity defects and nephrotic syndrome. Journal of the American Society of Nephrology, 20(4), 798-806. https://doi.org/10.1681/ASN.2008080871

MLA:

Huber, Tobias B., et al. "Loss of podocyte apkcλ/ι causes polarity defects and nephrotic syndrome." Journal of the American Society of Nephrology 20.4 (2009): 798-806.

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