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

Autor: Miguel Navarro, Wendell Girard-Dias, Antonio Barquilla, Paul N. Ulrich, Roberto Docampo, Sergio Schenkman, Kildare Miranda, Leonardo Augusto, Renata Rosito Tonelli, Veronica Jimenez, Sheila Cristina Nardelli, Maria Cristina M. Motta, Teresa Cristina Leandro de Jesus
Přispěvatelé: Univ Georgia, Universidade Federal de São Paulo (UNIFESP), Universidade Federal do Rio de Janeiro (UFRJ), Inst Nacl Metrol Normalizacao & Qualidade Ind, Consejo Super Invest Cient
Jazyk: angličtina
Rok vydání: 2010
Předmět:
Zdroj: Repositório Institucional da UNIFESP
Universidade Federal de São Paulo (UNIFESP)
instacron:UNIFESP
Repositório Institucional do INMETRO
Instituto Nacional de Metrologia, Qualidade e Tecnologia (INMETRO)
instacron:INMETRO
Popis: National Institutes of Health Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Ellison Medical Foundation to the Center for Tropical and Emerging Global Diseases American Heart Association 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. Univ Georgia, Ctr Trop & Emerging Global Dis, Athens, GA 30602 USA Univ Georgia, Dept Cellular Biol, Athens, GA 30602 USA Universidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, BR-04023062 São Paulo, Brazil Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, BR-21949900 Rio de Janeiro, Brazil Inst Nacl Metrol Normalizacao & Qualidade Ind, Diretoria Programas, BR-25250020 Rio de Janeiro, Brazil Consejo Super Invest Cient, Inst Parasitol & Biomed Lopez Neyra, Granada 18100, Spain Universidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, BR-04023062 São Paulo, Brazil National Institutes of Health: AI-077538 Web of Science
Databáze: OpenAIRE