Uptake of GABA in Trypanosoma cruzi

• Published in: The Journal of eukaryotic microbiology Vol. 62; no. 5; pp. 629 - 636
• Main Authors: Galvez Rojas, Robert L, Ahn, Il‐Young, Suárez Mantilla, Brian, Sant'Anna, Celso, Pral, Elizabeth Mieko Furusho, Silber, Ariel Mariano
• Format: Journal Article
• Language: English
• Published: United States Society of Protozoologists 01-09-2015; Blackwell Publishing Ltd
• Subjects: Active metabolite transporters; adenosine triphosphate; Adenosine Triphosphate - biosynthesis; adenosinetriphosphatase; amino acid transporters; Amino Acids - metabolism; Animals; biochemical pathways; Biological Transport - drug effects; cations; Chagas disease; chemotherapy; culture media; cytoplasm; etiological agents; Fluorescent Antibody Technique; gamma-aminobutyric acid; gamma-Aminobutyric Acid - metabolism; glutamic acid; Glutamic Acid - metabolism; Hydrogen-Ion Concentration; Na+/metabolite symporter; oligomycin; Oligomycins - pharmacology; parasites; potassium; Potassium - metabolism; protons; signal transduction; sodium; Sodium - metabolism; symporters; temperature; Trypanosoma cruzi; Trypanosoma cruzi - drug effects; Trypanosoma cruzi - metabolism; Trypanosoma cruzi - ultrastructure; vertebrates; Na+/metabolite symporter; Active metabolite transporters; amino acids metabolism; chemotherapy
• ISSN: 1066-5234; 1550-7408
• DOI: 10.1111/jeu.12219

Gamma aminobutyric acid (GABA) is widely known as a neurotransmitter and signal transduction molecule found in vertebrates, plants, and some protozoan organisms. However, the presence of GABA and its role in trypanosomatids is unknown. Here, we report the presence of intracellular GABA and the biochemical characterization of its uptake in Trypanosoma cruzi, the etiological agent of Chagas' disease. Kinetic parameters indicated that GABA is taken up by a single transport system in pathogenic and nonpathogenic forms. Temperature dependence assays showed a profile similar to glutamate transport, but the effect of extracellular cations Na⁺, K⁺, and H⁺ on GABA uptake differed, suggesting a different uptake mechanism. In contrast to reports for other amino acid transporters in T. cruzi, GABA uptake was Na⁺ dependent and increased with pH, with a maximum activity at pH 8.5. The sensitivity to oligomycin showed that GABA uptake is dependent on ATP synthesis. These data point to a secondary active Na⁺/GABA symporter energized by Na⁺‐exporting ATPase. Finally, we show that GABA occurs in the parasite's cytoplasm under normal culture conditions, indicating that it is regularly taken up from the culture medium or synthesized through an still undescribed metabolic pathway.