Duning, Kerstin and Rosenbusch, Deike and Schlueter, Marc A. and Tian, Yuemin and Kunzelmann, Karl and Meyer, Nina and Schulze, Ulf and Markoff, Arseni and Pavenstaedt, Hermann and Weide, Thomas (2010) Polycystin-2 Activity Is Controlled by Transcriptional Coactivator with PDZ Binding Motif and PALS1-associated Tight Junction Protein. JOURNAL OF BIOLOGICAL CHEMISTRY, 285 (44). pp. 33584-33588. ISSN 0021-9258,
Full text not available from this repository. (Request a copy)Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent monogenic cause of kidney failure, characterized by the development of renal cysts. ADPKD is caused by mutations of the polycystin-1 (PC1) or polycystin-2 (PC2) genes. PC2 encodes a Ca(2+)-permeable cation channel, and its dysfunction has been implicated in cyst development. The transcriptional coactivator with PDZ binding motif (TAZ) is required for the integrity of renal cilia. Its absence results in the development of renal cysts in a knock-out mouse model. TAZ directly interacts with PC2, and it has been suggested that another yet unidentified PDZ domain protein may be involved in the TAZ/PC2 interaction. Here we describe a novel interaction of TAZ with the multi-PDZ-containing PALS1-associated tight junction protein (PATJ). TAZ interacts with both the N-terminal PDZ domains 1-3 and the C-terminal PDZ domains 8-10 of PATJ, suggesting two distinct TAZ binding domains. We also show that the C terminus of PC2 strongly interacts with PDZ domains 8-10 and to a weaker extent with PDZ domains 1-3 of PATJ. Finally, we demonstrate that both TAZ and PATJ impair PC2 channel activity when co-expressed with PC2 in oocytes of Xenopus laevis. These results implicate TAZ and PATJ as novel regulatory elements of the PC2 channel and might thus be involved in ADPKD pathology.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MAMMALIAN EPITHELIAL-CELLS; KIDNEY-DISEASE; DIRECTIONAL MIGRATION; SIGNALING COMPLEX; CYSTIC-FIBROSIS; PRIMARY CILIUM; HIPPO PATHWAY; TAZ; CHANNEL; INAD; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Karl Kunzelmann |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Jul 2020 05:32 |
| Last Modified: | 08 Jul 2020 05:32 |
| URI: | https://pred.uni-regensburg.de/id/eprint/23993 |
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