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

被引:38
作者
Leandro de Jesus, Teresa Cristina [1 ,2 ,3 ]
Tonelli, Renata Rosito [3 ]
Nardelli, Sheila C. [3 ]
Augusto, Leonardo da Silva [3 ]
Motta, Maria Cristina M. [4 ]
Girard-Dias, Wendell [4 ]
Miranda, Kildare [4 ,5 ]
Ulrich, Paul [1 ,2 ]
Jimenez, Veronica [1 ,2 ]
Barquilla, Antonio [6 ]
Navarro, Miguel [6 ]
Docampo, Roberto [1 ,2 ]
Schenkman, Sergio [3 ]
机构
[1] Univ Georgia, Ctr Trop & Emerging Global Dis, Athens, GA 30602 USA
[2] Univ Georgia, Dept Cellular Biol, Athens, GA 30602 USA
[3] Univ Fed Sao Paulo, Dept Microbiol Imunol & Parasitol, BR-04023062 Sao Paulo, Brazil
[4] Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, BR-21949900 Rio De Janeiro, Brazil
[5] Inst Nacl Metrol Normalizacao & Qualidade Ind, Diretoria Programas, BR-25250020 Rio De Janeiro, Brazil
[6] Consejo Super Invest Cient, Inst Parasitol & Biomed Lopez Neyra, Granada 18100, Spain
基金
美国国家卫生研究院;
关键词
INDUCIBLE EXPRESSION SYSTEM; INORGANIC POLYPHOSPHATE; CELL-GROWTH; FKBP12-RAPAMYCIN-ASSOCIATED PROTEIN; RNA INTERFERENCE; SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI; ACIDIC VACUOLES; GENE-EXPRESSION; OSMOTIC-STRESS;
D O I
10.1074/jbc.M110.120212
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:24131 / 24140
页数:10
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