mTORC1 signalling mediates PI3K-dependent large lipid droplet accumulation in Drosophila ovarian nurse cells.
mTORC1 signalling mediates PI3K-dependent large lipid droplet accumulation in Drosophila ovarian nurse cells.
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DOI：
10.1242/bio.022210
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发表时间：
2017-05-15
期刊：
影响因子：
2.4
通讯作者：
Wilson C
中科院分区：
文献类型：
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作者：
Mensah LB;Goberdhan DCI;Wilson C
胰岛素和胰岛素样生长因子信号传导（IIS）主要由PI 3-激酶（PI 3 K）/PTEN/Akt激酶信号传导盒介导，是一种高度进化保守的途径，参与协调生长、发育、衰老和营养稳态与饮食摄入。除了通过雷帕霉素（mTOR）复合物1（mTORC 1）的机械靶标促进信号传导外，它还控制转录调节因子，该复合物1刺激蛋白质和其他大分子的生物合成，并驱动生物体生长。以前的研究表明，在果蝇卵巢的营养储存生殖细胞的护士细胞的激活磷酸化Akt（pAkt）的细胞质池控制Pten，IIS的拮抗剂，细胞自主调节大脂滴在这些细胞中的积累在卵子发生的后期阶段。在这里，我们表明，Pten突变诱导的大脂滴表型强烈抑制mTor功能被删除时。此外，缺乏Tsc 1或Tsc 2（负调节mTORC 1活性）的保育细胞也通过涉及Rheb（TSC 2的下游G蛋白靶点，正调节mTORC 1）的机制积累大脂滴。我们的结论是，IIS/mTORC 1信号的升高是必要的和足够的诱导大的脂滴形成在后期的护士细胞，这表明在脂滴生物合成方面的作用，除了控制脂质代谢的途径。总结：营养敏感mTORC 1信号通路介导升高的胰岛素依赖性PI 3 K对果蝇卵巢营养储存滋养细胞中大脂滴形成的影响
Insulin and insulin-like growth factor signalling (IIS), which is primarily mediated by the PI3-kinase (PI3K)/PTEN/Akt kinase signalling cassette, is a highly evolutionarily conserved pathway involved in co-ordinating growth, development, ageing and nutrient homeostasis with dietary intake. It controls transcriptional regulators, in addition to promoting signalling by mechanistic target of rapamycin (mTOR) complex 1 (mTORC1), which stimulates biosynthesis of proteins and other macromolecules, and drives organismal growth. Previous studies in nutrient-storing germline nurse cells of the Drosophila ovary showed that a cytoplasmic pool of activated phosphorylated Akt (pAkt) controlled by Pten, an antagonist of IIS, cell-autonomously regulates accumulation of large lipid droplets in these cells at late stages of oogenesis. Here, we show that the large lipid droplet phenotype induced by Pten mutation is strongly suppressed when mTor function is removed. Furthermore, nurse cells lacking either Tsc1 or Tsc2, which negatively regulate mTORC1 activity, also accumulate large lipid droplets via a mechanism involving Rheb, the downstream G-protein target of TSC2, which positively regulates mTORC1. We conclude that elevated IIS/mTORC1 signalling is both necessary and sufficient to induce large lipid droplet formation in late-stage nurse cells, suggesting roles for this pathway in aspects of lipid droplet biogenesis, in addition to control of lipid metabolism. Summary: Signalling by the nutrient-sensitive mTORC1 pathway mediates the effects of elevated insulin-dependent PI3K on large lipid droplet formation in nutrient-storing nurse cells of the Drosophila ovary.