Trypanosoma brucei eflornithine transporter AAT6 is a low-affinity low-selective transporter for neutral amino acids

Mathieu, Christoph; González Salgado, Amaia; Wirdnam, Corina; Meier, Stefan; Suter, Marianne; Inbar, Ehud; Mäser, Pascal; Zilberstein, Dan; Sigel, Erwin; Bütikofer, Peter; Rentsch, Doris (2014). Trypanosoma brucei eflornithine transporter AAT6 is a low-affinity low-selective transporter for neutral amino acids. Biochemical journal, 463(1), pp. 9-18. Portland Press 10.1042/BJ20140719

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Amino acid transporters are crucial for parasite survival since the cellular metabolism of parasitic protozoa depends on the uptake of exogenous amino acids. Amino acid transporters are also of high pharmacological relevance because they may mediate uptake of toxic amino acid analogues. In the present study we show that the eflornithine transporter AAT6 from Trypanosoma brucei (TbAAT6) mediates growth on neutral amino acids when expressed in Saccharomyces cerevisiae mutants. The transport was electrogenic and further analysed in Xenopus laevis oocytes. Neutral amino acids, proline analogues, eflornithine and acivicin induced inward currents. For proline, glycine and tryptophan the apparent affinities and maximal transport rates increased with more negative membrane potentials. Proline-induced currents were dependent on pH, but not on sodium. Although proline represents the primary energy source of T. brucei in the tsetse fly, down-regulation of TbAAT6-expression by RNAi showed that in culture TbAAT6 is not essential for growth of procyclic form trypanosomes in the presence of glucose or proline as energy source. TbAAT6-RNAi lines of both bloodstream and procyclic form trypanosomes showed reduced susceptibility to eflornithine, whereas the sensitivity to acivicin remained unchanged, indicating that acivicin enters the cell by more than one transporter

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Department of Biology > Institute of Plant Sciences (IPS)
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine
08 Faculty of Science > Department of Biology > Institute of Plant Sciences (IPS) > Molecular Plant Physiology
08 Faculty of Science > Department of Biology > Institute of Cell Biology

UniBE Contributor:

Mathieu, Christoph; González Salgado, Amaia; Wirdnam, Corina; Meier, Stefan; Suter, Marianne; Inbar, Ehud; Mäser, Pascal; Sigel, Erwin; Bütikofer, Peter and Rentsch, Doris

Subjects:

500 Science > 580 Plants (Botany)
500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0264-6021

Publisher:

Portland Press

Language:

English

Submitter:

Peter Alfred von Ballmoos-Haas

Date Deposited:

26 Sep 2014 10:33

Last Modified:

10 Jul 2017 16:07

Publisher DOI:

10.1042/BJ20140719

Uncontrolled Keywords:

acivicin, amino acids, eflornithine, electrophysiology, transporter, Trypanosoma brucei, Xenopus oocyte

BORIS DOI:

10.7892/boris.58728

URI:

https://boris.unibe.ch/id/eprint/58728

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