Mendes, Filipa and Wakefield, J. and Bachhuber, T. and Barroso, M. and Bebok, Z. and Penque, D. and Kunzelmann, Karl and Amaral, M. D. (2005) Establishment and characterization of a novel polarized MDCK epithelial cellular model for CFTR studies. CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 16 (4-6). pp. 281-290. ISSN 1015-8987, 1421-9778
Full text not available from this repository. (Request a copy)Abstract
F508del is the most common mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that is responsible for the genetic disease Cystic Fibrosis (CF). It results in a major failure of CFTR to traffic to the apical membrane of epithelial cells, where it should function as a chloride (Cl-) channel. Most studies on localization, processing and cellular trafficking of wild-type (wt) and F508del-CFTR have been performed in non-epithelial cells. Notwithstanding, polarized epithelial cells possess distinctly organized and regulated membrane trafficking pathways. We have used Madin-Darby canine kidney (MDCK) type II cells (proximal tubular cells which do not express endogenous CFTR) to generate novel epithelial, polarized cellular models stably expressing wt- or F508del-CFTR through transduction with recombinant lentiviral vectors. Characterization of these cell lines shows that wt-CFTR is correctly processed and apically localized, producing a cAMP-activated Cl-conductance. In contrast, F508del-CFTR is mostly detected in its immature form, localized intracellularly and producing only residual Cl- conductance. These novel cell lines constitute bona fide models and significantly improved resources to investigate the molecular mechanisms of polarized membrane traffic of wt- and F508del-CFTR in the same cellular background. They are also useful to identify/validate novel therapeutic compounds for CF. Copyright (c) 2005 S. Karger AG, Basel.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TRANSMEMBRANE CONDUCTANCE REGULATOR; CYSTIC-FIBROSIS; DELTA-F508 CFTR; CONFORMATIONAL MATURATION; PROTEIN EXPRESSION; CELLS; MEMBRANE; PATHWAY; LOCALIZATION; TRAFFICKING; CFTR; cystic fibrosis; polarized epithelial cells; MDCK cells |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Karl Kunzelmann |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 02 Jun 2021 04:36 |
| Last Modified: | 02 Jun 2021 04:36 |
| URI: | https://pred.uni-regensburg.de/id/eprint/36651 |
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