Target of Rapamycin (TOR)-like 1 Kinase Is Involved in the Control of Polyphosphate Levels and Acidocalcisome Maintenance in Trypanosoma brucei

• Published in: The Journal of biological chemistry 2010-07, Vol.285 (31), p.24131-24140
• Main Authors: de Jesus, Teresa Cristina Leandro, Tonelli, Renata Rosito, Nardelli, Sheila C., da Silva Augusto, Leonardo, Motta, Maria Cristina M., Girard-Dias, Wendell, Miranda, Kildare, Ulrich, Paul, Jimenez, Veronica, Barquilla, Antonio, Navarro, Miguel, Docampo, Roberto, Schenkman, Sergio
• Format: Article
• Language: English
• Subjects: Acidocalcisomes; Animals; Cell Biology; Cell Cycle; Cell Proliferation; Cytosol - metabolism; Diphosphates - chemistry; DNA, Kinetoplast - metabolism; Intracellular Signaling Peptides and Proteins - chemistry; Intracellular Signaling Peptides and Proteins - physiology; Microbiology; Models, Biological; Organelles - metabolism; Osmosis; Osmotic Stress; Parasite Metabolism; Polyphosphate; Polyphosphates - chemistry; Protein Structure, Tertiary; Protein-Serine-Threonine Kinases - chemistry; Protein-Serine-Threonine Kinases - physiology; Protozoan Proteins - metabolism; Pyrophosphate; RNA Interference (RNAi); Signal Transduction; TOR; TOR Serine-Threonine Kinases; Trypanosoma brucei; Trypanosoma brucei brucei - metabolism; Trypanosome
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M110.120212

Target of rapamycin (TOR) kinases are highly conserved protein kinases that integrate signals from nutrients and growth factors to coordinate cell growth and cell cycle progression. It has been previously described that two TOR kinases control cell growth in the protozoan parasite Trypanosoma brucei, the causative agent of African trypanosomiasis. Here we studied an unusual TOR-like protein named TbTOR-like 1 containing a PDZ domain and found exclusively in kinetoplastids. TbTOR-like 1 localizes to unique cytosolic granules. After hyperosmotic stress, the localization of the protein shifts to the cell periphery, different from other organelle markers. Ablation of TbTOR-like 1 causes a progressive inhibition of cell proliferation, producing parasites accumulating in the S/G2 phase of the cell cycle. TbTOR-like 1 knocked down cells have an increased area occupied by acidic vacuoles, known as acidocalcisomes, and are enriched in polyphosphate and pyrophosphate. These results suggest that TbTOR-like 1 might be involved in the control of acidocalcisome and polyphosphate metabolism in T. brucei.