University of Edinburgh , Queen's Medical Research Institute, University/BHF Centre for Cardiovascular Science, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
Open Biol. 2012 Jan;2(1):110031. doi: 10.1098/rsob.110031.
Multi-cellular organisms need to successfully link cell growth and metabolism to environmental cues during development. Insulin receptor-target of rapamycin (InR-TOR) signalling is a highly conserved pathway that mediates this link. Herein, we describe poly, an essential gene in Drosophila that mediates InR-TOR signalling. Loss of poly results in lethality at the third instar larval stage, but only after a stage of extreme larval longevity. Analysis in Drosophila demonstrates that Poly and InR interact and that poly mutants show an overall decrease in InR-TOR signalling, as evidenced by decreased phosphorylation of Akt, S6K and 4E-BP. Metabolism is altered in poly mutants, as revealed by microarray expression analysis and a decreased triglyceride : protein ratio in mutant animals. Intriguingly, the cellular distribution of Poly is dependent on insulin stimulation in both Drosophila and human cells, moving to the nucleus with insulin treatment, consistent with a role in InR-TOR signalling. Together, these data reveal that Poly is a novel, conserved (from flies to humans) mediator of InR signalling that promotes an increase in cell growth and metabolism. Furthermore, homology to small subunits of Elongator demonstrates a novel, unexpected role for this complex in insulin signalling.
多细胞生物在发育过程中需要成功地将细胞生长和代谢与环境线索联系起来。胰岛素受体-雷帕霉素靶蛋白 (InR-TOR) 信号通路是一种高度保守的途径，介导这种联系。本文描述了 Poly，这是果蝇中一个必需基因，介导 InR-TOR 信号。Poly 缺失会导致第三龄幼虫期的致死，但仅在经历一段极度长寿的幼虫期后才会发生。在果蝇中的分析表明 Poly 和 InR 相互作用，并且 poly 突变体显示出 InR-TOR 信号的整体下降，这表现为 Akt、S6K 和 4E-BP 的磷酸化减少。Poly 突变体中的代谢发生改变，这可以通过微阵列表达分析和突变动物中甘油三酯：蛋白质比值降低来揭示。有趣的是，Poly 的细胞分布依赖于果蝇和人细胞中的胰岛素刺激，用胰岛素处理后会转移到细胞核，这与 InR-TOR 信号通路的作用一致。总之，这些数据表明 Poly 是一种新型的、保守的（从果蝇到人类）InR 信号转导介质，它促进细胞生长和代谢的增加。此外，与 Elongator 的小亚基的同源性表明该复合物在胰岛素信号中具有新的、意想不到的作用。
