Grosch, Melanie and Brunner, Katrin and Ilyaskin, Alexandr and Schober, Michael and Staudner, Tobias and Schmied, Denise and Stumpp, Tina and Schmidt, Kerstin N. and Madej, M. Gregor and Pessoa, Thaissa D. and Othmen, Helga and Kubitza, Marion and Osten, Larissa and de Vries, Uwe and Mair, Magdalena M. and Somlo, Stefan and Moser, Markus and Kunzelmann, Karl and Ziegler, Christine and Haerteis, Silke and Korbmacher, Christoph and Witzgall, Ralph (2021) A polycystin-2 protein with modified channel properties leads to an increased diameter of renal tubules and to renal cysts. JOURNAL OF CELL SCIENCE, 134 (16): jcs259013. ISSN 0021-9533, 1477-9137
Full text not available from this repository. (Request a copy)Abstract
Mutations in the PKD2 gene cause autosomal-dominant polycystic kidney disease but the physiological role of polycystin-2, the protein product of PKD2, remains elusive. Polycystin-2 belongs to the transient receptor potential (TRP) family of non-selective cation channels. To test the hypothesis that altered ion channel properties of polycystin-2 compromise its putative role in a control circuit controlling lumen formation of renal tubular structures, we generated a mouse model in which we exchanged the pore loop of polycystin-2 with that of the closely related cation channel polycystin-2L1 (encoded by PKD2L1), thereby creating the protein polycystin2poreL1. Functional characterization of this mutant channel in Xenopus laevis oocytes demonstrated that its electrophysiological properties differed from those of polycystin-2 and instead resembled the properties of polycystin-2L1, in particular regarding its permeability for Ca2+ ions. Homology modeling of the ion translocation pathway of polycystin-2poreL1 argues for a wider pore in polycystin-2poreL1 than in polycystin-2. In Pkd2poreL1 knock-in mice in which the endogenous polycystin-2 protein was replaced by polycystin-2poreL1 the diameter of collecting ducts was increased and collecting duct cysts developed in a strain-dependent fashion.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | KIDNEY; CILIA; PKD2; IDENTIFICATION; CILIOGENESIS; INHIBITION; MEMBRANE; SUBUNIT; CELLS; Polycystin-2; PKD2; Autosomal-dominant polycystic kidney disease; Knock-in mice; Electrophysiology; Xenopus laevis oocytes; Tubular diameter; Lumen formation |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie > Prof. Dr. Christine Ziegler Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Karl Kunzelmann Biology, Preclinical Medicine > Institut für Anatomie > Lehrstuhl für Molekulare und zelluläre Anatomie > Prof. Dr. Ralph Witzgall |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Aug 2022 06:45 |
| Last Modified: | 22 Aug 2022 06:45 |
| URI: | https://pred.uni-regensburg.de/id/eprint/46269 |
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