Neph-Nephrin proteins bind the Par3-Par6-atypical protein kinase C (aPKC) complex to regulate podocyte cell polarity
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Neph-Nephrin proteins bind the Par3-Par6-atypical protein kinase C (aPKC) complex to regulate podocyte cell polarity. / 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.
In: J BIOL CHEM, Vol. 283, No. 34, 22.08.2008, p. 23033-8.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Neph-Nephrin proteins bind the Par3-Par6-atypical protein kinase C (aPKC) complex to regulate podocyte cell polarity
AU - Hartleben, Björn
AU - Schweizer, Heiko
AU - Lübben, Pauline
AU - Bartram, Malte P
AU - Möller, Clemens C
AU - Herr, Ronja
AU - Wei, Changli
AU - Neumann-Haefelin, Elke
AU - Schermer, Bernhard
AU - Zentgraf, Hanswalter
AU - Kerjaschki, Dontscho
AU - Reiser, Jochen
AU - Walz, Gerd
AU - Benzing, Thomas
AU - Huber, Tobias B
PY - 2008/8/22
Y1 - 2008/8/22
N2 - 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.
AB - 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.
KW - Adaptor Proteins, Signal Transducing
KW - Animals
KW - Cell Adhesion Molecules
KW - Cell Cycle Proteins
KW - Cell Polarity
KW - Humans
KW - Kidney Glomerulus
KW - Membrane Proteins
KW - Mice
KW - Mice, Inbred C57BL
KW - Podocytes
KW - Protein Kinase C
KW - Journal Article
KW - Research Support, N.I.H., Extramural
KW - Research Support, Non-U.S. Gov't
U2 - 10.1074/jbc.M803143200
DO - 10.1074/jbc.M803143200
M3 - SCORING: Journal article
C2 - 18562307
VL - 283
SP - 23033
EP - 23038
JO - J BIOL CHEM
JF - J BIOL CHEM
SN - 0021-9258
IS - 34
ER -