Target genes of insulin and TOR signaling in Drosophila

对细胞生长和分裂的适当调节对所有后生动物的发育至关重要。虽然人们对细胞周期进程的机制以及在单细胞环境中控制这一过程的信号知道得很多，但对于多细胞生物体的不同组织和器官系统如何相互作用以协调其生长却知之甚少。决定细胞和生物生长的一个关键因素是营养的可获得性，目前的建议集中在氨基酸在果蝇幼虫发育过程中的生长控制中的调节功能。虽然众所周知，蛋白质摄入是动物生长的主要因素，但有关氨基酸可获得性信息在体内被感知和传播的机制尚不清楚。例如，一种可能具有类似功能的分子，如葡萄糖的胰岛素或脂肪的瘦素，尚未被确定为氨基酸。最近在酵母和哺乳动物细胞中的研究表明，与磷脂酰肌醇激酶同源的TOR(雷帕霉素的靶标)的信号转导，控制着包括氨基酸在内的营养物质的翻译启动和细胞周期进程。Tor最初被确定为雷帕霉素的细胞内靶点，雷帕霉素是一种免疫抑制剂，可以阻止T细胞的增殖。虽然TOR还没有在果蝇中被鉴定出来，但进化上的考虑强烈支持它的存在，我们的假设是氨基酸通过TOR信号通路控制细胞的生长。为了测试这一点，我们将研究TOR蛋白在果蝇中的功能。

Proper regulation of cell growth and division is critical for development of all metazoans. Whereas much is known about the mechanics of cell cycle progression and the signals that control this process in a unicellular context, much less is known on how different tissues and organ systems of multicellular organisms interact to coordinate their growth. A crucial factor in determining cell and organismal growth is nutrient availability, and the current proposal focuses on the regulatory function of amino acids in growth control during Drosophila larval development. Although it is well recognized that protein intake is a dominant factor in animal growth, the mechanism by which information on amino acid availability is sensed and propagated throughout the body is unknown. For example, a molecule which may perform analogous function as insulin for glucose, or leptin for fat, has not been identified for amino acids. Recent studies in yeasts and mammalian cells have shown that signaling by TOR (target of rapamycin), which has homology to phosphatidylinositol kinases, controls translation initiation and cell cycle progression in response to nutrients, including amino acids. TOR was initially identified as an intracellular target of rapamycin, an immunosuppressant which blocks proliferation of T cells. Although TOR has not yet been identified in Drosophila, evolutionary considerations strongly argue for its presence, and our hypothesis is that amino acids control cell growth through the TOR signaling pathway. To test this, we will investigate the function of TOR proteins in Drosophila.