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J Am Soc Nephrol. 2009 Apr;20(4):798-806. doi: 10.1681/ASN.2008080871. Epub 2009 Mar 11.

Loss of podocyte aPKClambda/iota causes polarity defects and nephrotic syndrome.

Author information

1
Renal Division, University Hospital Freiburg, Breisacher Strasse 66, D-79106 Freiburg, Germany. tobias.huber@uniklinik-freiburg.de

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 aPKClambda/iota 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, aPKClambda/iota was primarily expressed in developing glomerular epithelial cells and podocyte foot processes. Interestingly, under physiologic conditions, aPKClambda/iota 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 aPKClambda/iota in the maintenance of slit diaphragms and podocyte foot processes, aPKClambda/iota 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 glomerular maintenance and development.

PMID:
19279126
PMCID:
PMC2663834
DOI:
10.1681/ASN.2008080871
[Indexed for MEDLINE]
Free PMC Article

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