| Loss of podocyte aPKClambda/iota causes polarity defects and nephrotic syndrome. | |
MedLine Citation:
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PMID: 19279126 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
Authors:
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Tobias B Huber; Bj?rn Hartleben; Kirstin Winkelmann; Lisa Schneider; Jan U Becker; Michael Leitges; Gerd Walz; Hermann Haller; Mario Schiffer |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-03-11 |
Journal Detail:
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Title: Journal of the American Society of Nephrology : JASN Volume: 20 ISSN: 1533-3450 ISO Abbreviation: J. Am. Soc. Nephrol. Publication Date: 2009 Apr |
Date Detail:
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Created Date: 2009-03-30 Completed Date: 2009-05-22 Revised Date: 2010-04-02 |
Medline Journal Info:
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Nlm Unique ID: 9013836 Medline TA: J Am Soc Nephrol Country: United States |
Other Details:
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Languages: eng Pagination: 798-806 Citation Subset: IM |
Affiliation:
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Renal Division, University Hospital Freiburg, Breisacher Strasse 66, D-79106 Freiburg, Germany. tobias.huber@uniklinik-freiburg.de |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Polarity / physiology* Death Gene Deletion * Isoenzymes / deficiency Kidney Glomerulus / enzymology, pathology, physiopathology Mice Mice, Knockout Nephrotic Syndrome / enzymology, genetics*, pathology, physiopathology* Podocytes / enzymology, physiology* Protein Kinase C / deficiency* Proteinuria / enzymology, genetics* |
| Chemical | |
Reg. No./Substance:
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0/Isoenzymes; EC 2.7.1.-/PKC-3 protein; EC 2.7.1.37/protein kinase C lambda; EC 2.7.11.13/Protein Kinase C |
| Comments/Corrections | |
Comment In:
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J Am Soc Nephrol. 2009 Apr;20(4):683-5
[PMID:
19321703]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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