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

The Biochemical journal

PubMedID: 24988048

Mathieu C, González Salgado A, Wirdnam C, Meier S, Suter Grotemeyer M, Inbar E, Mäser P, Zilberstein D, Sigel E, Bütikofer P, Rentsch D. Trypanosoma brucei eflornithine transporter AAT6 is a low affinity, low selective transporter for neutral amino acids. Biochem J. 2014;.
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 analogs. We now show that the eflornithine transporter AAT6 from Trypanosoma brucei mediates growth on neutral amino acids when expressed in Saccharomyces cerevisiae mutants. The transport was electrogenic and further analyzed in Xenopus laevis oocytes. Neutral amino acids, proline analogs, 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 is entering the cell by more than one transporter.