Genetic analysis of AMPK function in Drosophila

描述(申请人提供)：真核生物通过暂停合成代谢过程和利用储存的能量来容忍环境中营养供应的波动和细胞新陈代谢对营养的消耗。从酵母到哺乳动物，AMP激活的激酶(AMPK)是细胞能量储存的感受器，也是保存ATP的代谢开关的激活器。虽然AMPK在指导细胞新陈代谢中的关键作用已经得到了很好的证实，但对AMPK信号的上游调节因子和下游效应因子知之甚少。这些研究的目标是在果蝇中使用遗传学方法来识别AMPK信号通路的新成分。在具体目标1中，我将确定AMPK功能丧失和获得所导致的生长和代谢表型。在具体目标2中，我将进行遗传和生化分析，以确认AMPK与其假定的上游调节因子和下游底物之间的关系。在具体目标3中，我将对AMPK突变表型的抑制子和增强子进行遗传筛选，以发现AMPK信号通路的新成分。总而言之，这些研究应该会揭示一条抵制使用生化方法进行表征的重要途径。

DESCRIPTION (provided by applicant): Eukaryotes tolerate fluctuations in the environmental supply of nutrients and their consumption by cellular metabolism by suspending anabolic processes and utilizing stored energy. From yeast to mammals, the AMP-activated kinase (AMPK) serves as the sensor of cellular energy stores and the activator of metabolic switches that conserve ATP. While the key role of AMPK in directing cellular metabolism is well established, little is known about the upstream regulators and downstream effectors of AMPK signaling. The goal of these studies is to use a genetic approach in Drosophila to identify novel components of the AMPK signaling pathway. In specific aim 1, I will determine the growth and metabolic phenotypes resulting from loss- and gain-of-function of AMPK. In specific aim 2, I will perform genetic and biochemical analyses to confirm relationships between AMPK and its putative upstream regulators and downstream substrates. In specific aim 3, I will undertake a genetic screen for suppressors and enhancers of AMPK mutant phenotypes to discover novel components of the AMPK signaling pathway. Collectively, these studies should shed light on an important pathway that has resisted characterization using biochemical approaches.