Botelho, Hugo M. and Uliyakina, Inna and Awatade, Nikhil T. and Proena, Maria C. and Tischer, Christian and Sirianant, Lalida and Kunzelmann, Karl and Pepperkok, Rainer and Amaral, Margarida D. (2015) Protein Traffic Disorders: an Effective High-Throughput Fluorescence Microscopy Pipeline for Drug Discovery. SCIENTIFIC REPORTS, 5: 9038. ISSN 2045-2322,
Full text not available from this repository. (Request a copy)Abstract
Plasma membrane proteins are essential molecules in the cell which mediate interactions with the exterior milieu, thus representing key drug targets for present pharma. Not surprisingly, protein traffic disorders include a large range of diseases sharing the common mechanism of failure in the respective protein to reach the plasma membrane. However, specific therapies for these diseases are remarkably lacking. Herein, we report a robust platform for drug discovery applied to a paradigmatic genetic disorder affecting intracellular trafficking - Cystic Fibrosis. This platform includes (i) two original respiratory epithelial cellular models incorporating an inducible double-tagged traffic reporter; (ii) a plasma membrane protein traffic assay for high-throughput microscopy screening; and (iii) open-source image analysis software to quantify plasma membrane protein traffic. By allowing direct scoring of compounds rescuing the basic traffic defect, this platform enables an effective drug development pipeline, which can be promptly adapted to any traffic disorder-associated protein and leverage therapy development efforts.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TRANSMEMBRANE CONDUCTANCE REGULATOR; CYSTIC-FIBROSIS; ENDOPLASMIC-RETICULUM; REVERSE TRANSFECTION; AIRWAY EPITHELIA; MUTANT CFTR; IN-VITRO; MUTATION; RECEPTOR; GENE; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Karl Kunzelmann |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Jul 2019 14:14 |
| Last Modified: | 22 Jul 2019 14:14 |
| URI: | https://pred.uni-regensburg.de/id/eprint/5793 |
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