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Sci Rep ; 7: 41619, 2017 02 08.
Article in English | MEDLINE | ID: mdl-28176814

ABSTRACT

The absorption, distribution, metabolism and excretion (ADME) of metabolites and toxic organic solutes are orchestrated by the ATP-binding cassette (ABC) transporters and the organic solute carrier family (SLC) proteins. A large number of ABC and SLC transpoters exist; however, only a small number have been well characterized. To facilitate the analysis of these transporters, which is important for drug safety and physiological studies, we developed a sensitive genetically encoded bilirubin (BR)-inducible fluorescence sensor (eUnaG) to detect transporter-coupled influx/efflux of organic compounds. This sensor can be used in live cells to measure transporter activity, as excretion of BR depends on ABC and SLC transporters. Applying eUnaG in functional RNAi screens, we characterize l(2)03659 as a Drosophila multidrug resistant-associated ABC transporter.


Subject(s)
Bilirubin/metabolism , Biosensing Techniques , Drug Discovery , Genes, Reporter , Ligands , Membrane Transport Proteins/genetics , Membrane Transport Proteins/metabolism , ATP-Binding Cassette Transporters/chemistry , ATP-Binding Cassette Transporters/genetics , ATP-Binding Cassette Transporters/metabolism , Animals , Biological Transport , Drosophila , Gene Expression , Humans , Membrane Transport Proteins/chemistry , Mitochondria/drug effects , Mitochondria/metabolism , Models, Molecular , Protein Conformation , Recombinant Fusion Proteins/chemistry , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism , Stress, Physiological , Structure-Activity Relationship
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