Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-8028, USA.
J Cell Sci. 2012 Jan 1;125(Pt 1):37-48. doi: 10.1242/jcs.077040. Epub 2012 Jan 20.
The TOR protein kinase functions in two distinct complexes, TOR complex 1 (TORC1) and 2 (TORC2). TORC1 is required for growth in response to growth factors, nutrients and the cellular energy state; TORC2 regulates AKT signaling, which can modulate cytoskeletal polarization. In its ecological niche, Dictyostelium engulf bacteria and yeast for nutrient capture. Despite the essential role of TORC1 in control of cellular growth, we show that nutrient particle capture (phagocytosis) in Dictyostelium is independent of TORC1-mediated nutrient sensing and growth regulation. However, loss of Dictyostelium TORC2 components Rictor/Pia, SIN1/RIP3 and Lst8 promotes nutrient particle uptake; inactivation of TORC2 leads to increased efficiency and speed of phagocytosis. In contrast to phagocytosis, we show that macropinocytosis, an AKT-dependent process for cellular uptake of fluid phase nutrients, is not regulated by either of the TOR complexes. The integrated and balanced regulation of TORC1 and TORC2 might be crucial in Dictyostelium to coordinate growth and energy needs with other essential TOR-regulated processes.
TOR 蛋白激酶存在于两个不同的复合物中，TOR 复合物 1（TORC1）和 2（TORC2）。TORC1 对于响应生长因子、营养物质和细胞能量状态的生长是必需的；TORC2 调节 AKT 信号通路，该信号通路可以调节细胞骨架极化。在其生态位中，Dictyostelium 吞噬细菌和酵母以捕获营养物质。尽管 TORC1 在控制细胞生长方面起着至关重要的作用，但我们发现，Dictyostelium 中的营养颗粒捕获（吞噬作用）独立于 TORC1 介导的营养感应和生长调节。然而，Dictyostelium 的 TORC2 成分 Rictor/Pia、SIN1/RIP3 和 Lst8 的缺失会促进营养颗粒的摄取；TORC2 的失活会导致吞噬作用的效率和速度增加。与吞噬作用相反，我们表明，细胞对流体营养物质的摄取的 AKT 依赖性过程——巨胞饮作用，不受任何一个 TOR 复合物的调节。TORC1 和 TORC2 的综合和平衡调节可能对协调生长和能量需求与其他必需的 TOR 调节过程至关重要。
