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Am J Physiol Renal Physiol. 2016 Jul 1;311(1):F112-9. doi: 10.1152/ajprenal.00171.2016. Epub 2016 Apr 27.

Par3A is dispensable for the function of the glomerular filtration barrier of the kidney.

Author information

1
Department II of Internal Medicine, University Hospital of Cologne, Cologne, Germany; Center for Molecular Medicine, University of Cologne, Cologne, Germany;
2
Center for Molecular Medicine, University of Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany; Department of Dermatology, University Hospital of Cologne, Cologne, Germany;
3
Department of Molecular and Cellular Sport Medicine, Institute of Cardiovascular Research and Sport Medicine, German Sport University Cologne, Cologne, Germany, and.
4
Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria.
5
Department II of Internal Medicine, University Hospital of Cologne, Cologne, Germany; Center for Molecular Medicine, University of Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany; Systems Biology of Ageing Cologne (Sybacol), University of Cologne, Cologne, Germany;
6
Department II of Internal Medicine, University Hospital of Cologne, Cologne, Germany; Center for Molecular Medicine, University of Cologne, Cologne, Germany; paul.brinkkoetter@uk-koeln.de.

Abstract

Polarity signaling through the atypical PKC (aPKC)-Par polarity complex is essential for the development and maintenance of the podocyte architecture and the function of the glomerular filtration barrier of the kidney. To study the contribution of Par3A in this complex, we generated a novel Pard3 podocyte-specific knockout mouse model by targeting exon 6 of the Pard3 gene. Genetic deletion of Pard3a did not impair renal function, neither at birth nor later in life. Even challenging the animals did not result in glomerular disease. Despite its well-established role in aPKC-mediated signaling, Par3A appears to be dispensable for the function of the glomerular filtration barrier. Moreover, its homolog Pard3b, and not Pard3a, is the dominant Par3 gene expressed in podocytes and found at the basis of the slit diaphragm, where it partially colocalizes with podocin. In conclusion, Par3A function is either dispensable for slit diaphragm integrity, or compensatory mechanisms and a high redundancy of the different polarity proteins, including Par3B, Lgl, or PALS1, maintain the function of the glomerular filtration barrier, even in the absence of Par3A.

KEYWORDS:

aPKC-Par complex; podocyte; polarity; slit diaphragm

PMID:
27122542
DOI:
10.1152/ajprenal.00171.2016
[Indexed for MEDLINE]
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