Neph-nephrin proteins bind the Par3-Par6-atypical protein kinase C (aPKC) complex to regulate podocyte cell polarity

Björn Hartleben, Heiko Schweizer, Pauline Lübben, Malte P. Bartram, Clemens C. Möller, Ronja Herr, Changli Wei, Elke Neumann-Haefelin, Bernhard Schermer, Hanswalter Zentgraf, Dontscho Kerjaschki, Jochen Reiser, Gerd Walz, Thomas Benzing, Tobias B. Huber

Research output: Contribution to journalArticlepeer-review

91 Scopus citations

Abstract

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 Par 3 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.

Original languageEnglish (US)
Pages (from-to)23033-23038
Number of pages6
JournalJournal of Biological Chemistry
Volume283
Issue number34
DOIs
StatePublished - Aug 22 2008
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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