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雷帕霉素靶蛋白(TOR)样激酶 1 参与调控布鲁氏锥虫多磷酸盐水平和液泡内钙储存。

Target of rapamycin (TOR)-like 1 kinase is involved in the control of polyphosphate levels and acidocalcisome maintenance in Trypanosoma brucei.

机构信息

Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, São Paulo 04023-062, Brazil.

出版信息

J Biol Chem. 2010 Jul 30;285(31):24131-40. doi: 10.1074/jbc.M110.120212. Epub 2010 May 21.

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.

摘要

雷帕霉素靶蛋白(TOR)激酶是高度保守的蛋白激酶,可整合来自营养物质和生长因子的信号,以协调细胞生长和细胞周期进程。先前已经描述了两种 TOR 激酶控制非洲锥虫病病原体布氏锥虫中的细胞生长。在这里,我们研究了一种名为 TbTOR-like 1 的不寻常的 TOR 样蛋白,它含有 PDZ 结构域,并且仅存在于动基体门生物中。TbTOR-like 1 定位于独特的细胞质颗粒中。在高渗胁迫后,该蛋白的定位转移到细胞外周,与其他细胞器标记物不同。TbTOR-like 1 的缺失导致细胞增殖的逐渐抑制,产生在细胞周期的 S/G2 期积累的寄生虫。TbTOR-like 1 敲低的细胞酸性液泡(称为酸钙小球)占据的面积增加,并且富含多磷酸盐和焦磷酸盐。这些结果表明,TbTOR-like 1 可能参与控制布氏锥虫中的酸钙小球和多磷酸盐代谢。

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