Par3A is dispensable for the function of the glomerular filtration barrier of the kidney.
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.
Department II of Internal Medicine, University Hospital of Cologne, Cologne, Germany; Center for Molecular Medicine, University of Cologne, Cologne, Germany;
Sybille
S
Koehler
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;
Frederik
F
Tellkamp
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;
Carien M
CM
Niessen
Department of Molecular and Cellular Sport Medicine, Institute of Cardiovascular Research and Sport Medicine, German Sport University Cologne, Cologne, Germany, and.
Wilhelm
W
Bloch
Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria.
Dontscho
D
Kerjaschki
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;
Bernhard
B
Schermer
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;
Thomas
T
Benzing
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.
Paul T
PT
Brinkkoetter
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D005260:Female; D060730:Glomerular Filtration Barrier / Q000502:physiology*; D007668:Kidney / Q000473:pathology / Q000502:physiology*; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009703:Nucleoside-Phosphate Kinase / Q000235:genetics / Q000378:metabolism; D050199:Podocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D061251:Primary Cell Culture; D012710:Serum Albumin, Bovine / Q000633:toxicity
D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; D008070:Lipopolysaccharides; D008565:Membrane Proteins; C115084:Pard3 protein, mouse; D012710:Serum Albumin, Bovine; D009703:Nucleoside-Phosphate Kinase; C499979:Mpp5 protein, mouse
aPKC-Par complex; podocyte; polarity; slit diaphragm