KIBRA modulates directional migration of podocytes
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KIBRA modulates directional migration of podocytes. / Duning, Kerstin; Schurek, Eva-Maria; Schlüter, Marc; Bayer, Michael; Reinhardt, Hans-Christian; Schwab, Albrecht; Schaefer, Liliana; Benzing, Thomas; Schermer, Bernhard; Saleem, Moin A; Huber, Tobias B; Bachmann, Sebastian; Kremerskothen, Joachim; Weide, Thomas; Pavenstädt, Hermann.
in: J AM SOC NEPHROL, Jahrgang 19, Nr. 10, 10.2008, S. 1891-903.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - KIBRA modulates directional migration of podocytes
AU - Duning, Kerstin
AU - Schurek, Eva-Maria
AU - Schlüter, Marc
AU - Bayer, Michael
AU - Reinhardt, Hans-Christian
AU - Schwab, Albrecht
AU - Schaefer, Liliana
AU - Benzing, Thomas
AU - Schermer, Bernhard
AU - Saleem, Moin A
AU - Huber, Tobias B
AU - Bachmann, Sebastian
AU - Kremerskothen, Joachim
AU - Weide, Thomas
AU - Pavenstädt, Hermann
PY - 2008/10
Y1 - 2008/10
N2 - Asymmetric delivery and distribution of macromolecules are essential for cell polarity and for cellular functions such as differentiation, division, and signaling. Injury of podocytes, which are polarized epithelial cells, changes the dynamics of the actin meshwork, resulting in foot process retraction and proteinuria. Although the spatiotemporal control of specific protein-protein interactions is crucial for the establishment of cell polarity, the mechanisms controlling polarity-dependent differentiation and division are incompletely understood. In this study, yeast two-hybrid screens were performed using a podocyte cDNA library and the polarity protein PATJ as bait. The protein KIBRA was identified as an interaction partner of PATJ and was localized to podocytes, tubular structures, and collecting ducts. The last four amino acids of KIBRA mediated binding to the eighth PDZ domain of PATJ. In addition, KIBRA directly bound to synaptopodin, an essential organizer of the podocyte cytoskeleton. Stable knockdown of KIBRA in immortalized podocytes impaired directed cell migration, suggesting that KIBRA modulates the motility of podocytes by linking polarity proteins and cytoskeleton-associated protein complexes.
AB - Asymmetric delivery and distribution of macromolecules are essential for cell polarity and for cellular functions such as differentiation, division, and signaling. Injury of podocytes, which are polarized epithelial cells, changes the dynamics of the actin meshwork, resulting in foot process retraction and proteinuria. Although the spatiotemporal control of specific protein-protein interactions is crucial for the establishment of cell polarity, the mechanisms controlling polarity-dependent differentiation and division are incompletely understood. In this study, yeast two-hybrid screens were performed using a podocyte cDNA library and the polarity protein PATJ as bait. The protein KIBRA was identified as an interaction partner of PATJ and was localized to podocytes, tubular structures, and collecting ducts. The last four amino acids of KIBRA mediated binding to the eighth PDZ domain of PATJ. In addition, KIBRA directly bound to synaptopodin, an essential organizer of the podocyte cytoskeleton. Stable knockdown of KIBRA in immortalized podocytes impaired directed cell migration, suggesting that KIBRA modulates the motility of podocytes by linking polarity proteins and cytoskeleton-associated protein complexes.
KW - Cell Culture Techniques
KW - Cell Movement
KW - Cell Polarity
KW - Cytoskeletal Proteins
KW - Gene Library
KW - Humans
KW - Intracellular Signaling Peptides and Proteins
KW - Membrane Proteins
KW - Phosphoproteins
KW - Podocytes
KW - Protein Binding
KW - Proteins
KW - RNA, Messenger
KW - Tight Junction Proteins
KW - Two-Hybrid System Techniques
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1681/ASN.2007080916
DO - 10.1681/ASN.2007080916
M3 - SCORING: Journal article
C2 - 18596123
VL - 19
SP - 1891
EP - 1903
JO - J AM SOC NEPHROL
JF - J AM SOC NEPHROL
SN - 1046-6673
IS - 10
ER -