Target genes of insulin and TOR signaling in Drosophila

果蝇胰岛素和 TOR 信号传导的靶基因

• 批准号: 5280953
• 负责人: Professor Dr. Michael Pankratz
• 金额: --
• 依托单位: Abteilung Molekulare Hirnphysiologie und Verhaltensforschung
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2000
• 资助国家: 德国
• 起止时间: 1999-12-31 至 2010-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5280953?language=en
• 关键词: Target; genes; insulin; TOR; signaling

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.

细胞生长和分裂的适当调节对于所有后生动物的发育至关重要。虽然我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了解很多，但对多细胞生物的不同组织和器官系统如何相互作用以协调其生长的了解要少得多。决定细胞和有机体生长的一个关键因素是营养物质的可用性，目前的建议集中在果蝇幼虫发育过程中生长控制中氨基酸的调节功能。虽然人们普遍认为蛋白质摄入是动物生长的主要因素，但关于氨基酸可用性的信息在整个身体中被感知和传播的机制尚不清楚。例如，对于氨基酸，还没有鉴定出一种分子，它可以像胰岛素对葡萄糖或瘦素对脂肪那样发挥类似的功能。最近在酵母和哺乳动物细胞中的研究表明，与磷脂酰肌醇激酶具有同源性的TOR（雷帕霉素的靶标）的信号传导控制响应于营养物（包括氨基酸）的翻译起始和细胞周期进展。TOR最初被鉴定为雷帕霉素的细胞内靶标，雷帕霉素是一种阻断T细胞增殖的免疫抑制剂。虽然TOR尚未在果蝇中被发现，但进化方面的考虑强烈支持它的存在，我们的假设是氨基酸通过TOR信号通路控制细胞生长。为了验证这一点，我们将研究果蝇中TOR蛋白的功能。