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Target of Rapamycin (TOR)-like 1 Kinase Is Involved in the Control of Polyphosphate Levels and Acidocalcisome Maintenance in Trypanosoma brucei
Authors:Teresa Cristina Leandro de Jesus  Renata Rosito Tonelli  Sheila C. Nardelli  Leonardo da Silva Augusto  Maria Cristina M. Motta  Wendell Girard-Dias  Kildare Miranda  Paul Ulrich  Veronica Jimenez  Antonio Barquilla  Miguel Navarro  Roberto Docampo  Sergio Schenkman
Abstract: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.
Keywords:Cell Cycle   Parasite Metabolism   RNA Interference (RNAi)   TOR   Trypanosome   Acidocalcisomes   Osmotic Stress   Polyphosphate   Trypanosoma brucei   Pyrophosphate
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