National Creative Research Initiatives Center for Energy Homeostasis Regulation and Institute of Molecular Biology and Genetics, Seoul National University, Seoul 08826, Republic of Korea.
National Creative Research Initiatives Center for Energy Homeostasis Regulation and Institute of Molecular Biology and Genetics, Seoul National University, Seoul 08826, Republic of Korea; School of Biological Sciences, Seoul National University, Seoul 08826, Republic of Korea.
Dev Cell. 2017 Aug 21;42(4):363-375.e4. doi: 10.1016/j.devcel.2017.07.020.
Target of rapamycin complex 1 (TORC1) regulates cell growth in response to nutrients and growth factors. Although TORC1 signaling has been thoroughly studied at the cellular level, the regulation of TORC1 in multicellular tissues and organs has remained elusive. Here we found that TORC1 is selectively activated in the second mitotic wave (SMW), the terminal synchronous cell division, of the developing Drosophila eye. We demonstrated that Hedgehog (Hh) signaling regulates TORC1 through E2F1 and the cyclin D/Cdk4 complex in the SMW, and this regulation is independent from insulin and amino acid signaling pathways. TORC1 is necessary for the proper G1/S transition of the cells, and the activation of TORC1 rescues the cell-cycle defect of Hh signaling-deficient cells in the SMW. Based on this evolutionarily conserved regulation of TORC1 by Hh signaling, we propose that Hh-dependent developmental signaling pathways spatially regulate TORC1 activity in multicellular organisms.
雷帕霉素靶蛋白复合物 1（TORC1）可响应营养物质和生长因子调节细胞生长。尽管 TORC1 信号已在细胞水平上得到深入研究，但 TORC1 在多细胞组织和器官中的调节仍难以捉摸。在这里，我们发现 TORC1 在发育中的果蝇眼的第二次有丝分裂波（SMW）中被选择性激活，这是终末同步细胞分裂。我们证明 Hedgehog（Hh）信号通过 E2F1 和细胞周期蛋白 D/Cdk4 复合物在 SMW 中调节 TORC1，这种调节独立于胰岛素和氨基酸信号通路。TORC1 对于细胞的适当 G1/S 转变是必要的，并且 TORC1 的激活挽救了 SMW 中 Hh 信号缺失细胞的细胞周期缺陷。基于 Hh 信号对 TORC1 的这种进化上保守的调节，我们提出 Hh 依赖性发育信号通路在多细胞生物中空间调节 TORC1 活性。
