Neph-Nephrin Proteins Bind the Par3-Par6-Atypical Protein Kinase C (aPKC) Complex to Regulate Podocyte Cell Polarity

The kidney filter represents a unique assembly of podocyte epithelial cells that tightly enwrap the glomerular capillaries with their foot processes and the interposed slit diaphragm. So far, very little is known about the guidance cues and polarity signals required to regulate proper development an...

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Bibliographic Details
Published in:The Journal of biological chemistry 2008-08, Vol.283 (34), p.23033-23038
Main Authors: Hartleben, Björn, Schweizer, Heiko, Lübben, Pauline, Bartram, Malte P., Möller, Clemens C., Herr, Ronja, Wei, Changli, Neumann-Haefelin, Elke, Schermer, Bernhard, Zentgraf, Hanswalter, Kerjaschki, Dontscho, Reiser, Jochen, Walz, Gerd, Benzing, Thomas, Huber, Tobias B.
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - chemistry
Animals
Cell Adhesion Molecules - chemistry
Cell Cycle Proteins - chemistry
Cell Polarity
Humans
Kidney Glomerulus - metabolism
Membrane Proteins - chemistry
Membrane Proteins - physiology
Mice
Mice, Inbred C57BL
Molecular Basis of Cell and Developmental Biology
Podocytes - cytology
Protein Kinase C - chemistry
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Summary:The kidney filter represents a unique assembly of podocyte epithelial cells that tightly enwrap the glomerular capillaries with their foot processes and the interposed slit diaphragm. So far, very little is known about the guidance cues and polarity signals required to regulate proper development and maintenance of the glomerular filtration barrier. We now identify Par3, Par6, and atypical protein kinase C (aPKC) polarity proteins as novel Neph1-Nephrin-associated proteins. The interaction was mediated through the PDZ domain of Par3 and conserved carboxyl terminal residues in Neph1 and Nephrin. Par3, Par6, and aPKC localized to the slit diaphragm as shown in immunofluorescence and immunoelectron microscopy. Consistent with a critical role for aPKC activity in podocytes, inhibition of glomerular aPKC activity with a pseudosubstrate inhibitor resulted in a loss of regular podocyte foot process architecture. These data provide an important link between cell recognition mediated through the Neph1-Nephrin complex and Par-dependent polarity signaling and suggest that this molecular interaction is essential for establishing the three-dimensional architecture of podocytes at the kidney filtration barrier.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M803143200