Arginine and lysine transporters are essential for Trypanosoma brucei
| Autor: | Daniel Hürlimann, Peter Bütikofer, Doris Rentsch, Amaia Gonzalez-Salgado, Corina Wirdnam, Christoph Mathieu, Alexander C. Haindrich, Remo S. Schmidt, Ehud Inbar, Pascal Mäser, Marianne Suter Grotemeyer, Juan Pereira de Macêdo, Dan Zilberstein |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Arginine Xenopus Lysine Protozoan Proteins lcsh:Medicine Yeast and Fungal Models 580 Plants (Botany) Biochemistry Xenopus laevis chemistry.chemical_compound RNA interference Amino Acids 610 Medicine & health lcsh:Science Phylogeny Protozoans Trypanosoma Cruzi chemistry.chemical_classification Thialysine Multidisciplinary biology Organic Compounds Animal Models Amino acid Nucleic acids Chemistry Experimental Organism Systems Genetic interference Physical Sciences Xenopus Oocytes Vertebrates Saccharomyces Cerevisiae Frogs Epigenetics Basic Amino Acids Canavanine Research Article Lysine transport Trypanosoma Trypanosoma brucei brucei Trypanosoma brucei Research and Analysis Methods complex mixtures Amphibians Saccharomyces Open Reading Frames 03 medical and health sciences Model Organisms Genetics Animals Humans Histidine Permease lcsh:R Organic Chemistry Chemical Compounds Organisms Fungi Biology and Life Sciences Proteins biology.organism_classification Homoarginine Molecular biology Parasitic Protozoans Yeast Kinetics 030104 developmental biology chemistry Oocytes 570 Life sciences RNA Amino Acid Transport Systems Basic bacteria lcsh:Q Gene expression Trypanosoma Brucei Gambiense |
| Zdroj: | PLoS ONE Mathieu, Christoph; Pereira de Macêdo, Juan; Hürlimann, Daniel; Wirdnam, Corina; Haindrich, Alexander; Suter, Marianne; González Salgado, Amaia; Schmidt, Remo; Inbar, Ehud; Mäser, Pascal; Bütikofer, Peter; Zilberstein, Dan; Rentsch, Doris (2017). Arginine and Lysine Transporters Are Essential for Trypanosoma brucei. PLoS ONE, 12(1), e0168775. Public Library of Science 10.1371/journal.pone.0168775 PLoS ONE, Vol 12, Iss 1, p e0168775 (2017) |
| DOI: | 10.5451/unibas-ep52947 |
| Popis: | For Trypanosoma brucei arginine and lysine are essential amino acids and therefore have to be imported from the host. Heterologous expression in Saccharomyces cerevisiae mutants identified cationic amino acid transporters among members of the T. brucei AAAP (amino acid/auxin permease) family. TbAAT5-3 showed high affinity arginine uptake (Km 3.6 ± 0.4 μM) and high selectivity for L-arginine. L-arginine transport was reduced by a 10-times excess of L-arginine, homo-arginine, canavanine or arginine-β-naphthylamide, while lysine was inhibitory only at 100-times excess, and histidine or ornithine did not reduce arginine uptake rates significantly. TbAAT16-1 is a high affinity (Km 4.3 ± 0.5 μM) and highly selective L-lysine transporter and of the compounds tested, only L-lysine and thialysine were competing for L-lysine uptake. TbAAT5-3 and TbAAT16-1 are expressed in both procyclic and bloodstream form T. brucei and cMyc-tagged proteins indicate localization at the plasma membrane. RNAi-mediated down-regulation of TbAAT5 and TbAAT16 in bloodstream form trypanosomes resulted in growth arrest, demonstrating that TbAAT5-mediated arginine and TbAAT16-mediated lysine transport are essential for T. brucei. Growth of induced RNAi lines could partially be rescued by supplementing a surplus of arginine or lysine, respectively, while addition of both amino acids was less efficient. Single and double RNAi lines indicate that additional low affinity uptake systems for arginine and lysine are present in T. brucei. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|