title: Target of rapamycin (TOR)-like 1 kinase is involved in the control of polyphosphate levels and acidocalcisome maintenance in Trypanosoma brucei.
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/G(2) 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.
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, São Paulo 04023-062, Brazil.
authors.forename: Teresa Cristina Leandro
authors.initials: TC
authors.lastname: de Jesus
authors.forename: Renata Rosito
authors.initials: RR
authors.lastname: Tonelli
authors.forename: Sheila C
authors.initials: SC
authors.lastname: Nardelli
authors.forename: Leonardo
authors.initials: L
authors.lastname: da Silva Augusto
authors.forename: Maria Cristina M
authors.initials: MC
authors.lastname: Motta
authors.forename: Wendell
authors.initials: W
authors.lastname: Girard-Dias
authors.forename: Kildare
authors.initials: K
authors.lastname: Miranda
authors.forename: Paul
authors.initials: P
authors.lastname: Ulrich
authors.forename: Veronica
authors.initials: V
authors.lastname: Jimenez
authors.forename: Antonio
authors.initials: A
authors.lastname: Barquilla
authors.forename: Miguel
authors.initials: M
authors.lastname: Navarro
authors.forename: Roberto
authors.initials: R
authors.lastname: Docampo
authors.forename: Sergio
authors.initials: S
authors.lastname: Schenkman
mesh_terms: D000818:Animals; D002453:Cell Cycle; D049109:Cell Proliferation; D003600:Cytosol / Q000378:metabolism; D018105:DNA, Kinetoplast / Q000378:metabolism; D011756:Diphosphates / Q000737:chemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000502:physiology*; D008954:Models, Biological; D015388:Organelles / Q000378:metabolism; D009995:Osmosis; D011122:Polyphosphates / Q000737:chemistry*; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000502:physiology*; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases; D014346:Trypanosoma brucei brucei / Q000378:metabolism*
chemical_list: D018105:DNA, Kinetoplast; D011756:Diphosphates; D047908:Intracellular Signaling Peptides and Proteins; D011122:Polyphosphates; D015800:Protozoan Proteins; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases