An aminoacyl tRNA synthetase is a nitrogen sensor that activates TOR in plants

项目摘要：真核生物的生长受TOR调节，TOR是一种由氨基激活的激酶 酸和葡萄糖，然后广泛促进合成代谢，包括蛋白质，脂肪和核苷酸 综合。Tor失调导致或促成了包括癌症在内的一系列人类疾病， 肥胖、病毒感染、糖尿病、衰老和神经退化。ToR信号处于紧张状态 酵母和动物细胞生物学家的研究，他们试图描述 控制TOR信号网络，以便开发微调TOR活动的治疗方法 治疗人类疾病。对其他主要的TOR信令网络的了解要少得多 真核生物谱系，植物。这个项目使用了遗传、生化、基因组和 蛋白质组学方法来继续我最近对一种氨基酸传感器的突破性发现 激活植物细胞中的TOR。之前还没有在植物中发现氨基酸传感器的特征， 虽然氨基酸是许多天然土壤中发现的氮的主要形式，但氨基酸 是大多数植物器官间氮素的主要运输形式。理解 植物如何感知和响应氮素是植物分子生物学家的首要任务，因为 全球农作物产量在很大程度上依赖于大量使用对环境有害且昂贵的 石化化肥。这项对激活TOR的氮传感器的拟议调查将 实现智能育种努力，以生产能够在低成本条件下获得高产的作物 通过调节植物的氮素感知机制来调节氮素环境。的第一个具体目标 该项目首先确定氮源如何影响TOR活性，然后确认 所提出的氨基酸传感器，一种氨基酰基tRNA合成酶，确实作用于TOR信号的上游。 该项目的第二个目标是使用强大的当代蛋白质组学技术来识别 与TOR和/或拟议的氮传感器相互作用以控制氮介导的蛋白质 使用强大的蛋白质组学技术激活ToR。最后，提出了氮传感器的作用 在植物发育方面，将探讨作物产量和对环境氮源的反应。 在几个最重要的全球农作物物种中。通过这种创新的方法来探索如何 氨基酸感应机制已经随着真核生物中的TOR信号而进化，这个项目将 同时促进对植物如何协调生长和发育的理解 氮的有效性，并提供了对氨基酸-TOR网络的原创性见解，这些网络将受益 人类TOR细胞生物学的生物医学研究。

PROJECT SUMMARY: Eukaryotic growth is regulated by TOR, a kinase that is activated by amino acids and glucose and then broadly promotes anabolism, including protein, lipid, and nucleotide synthesis. TOR dysregulation causes or contributes to an array of human diseases, including cancer, obesity, viral infections, diabetes, aging, and neurodegeneration. TOR signaling is under intense investigation among yeast and animal cell biologists, who seek to characterize the mechanisms that control TOR signaling networks in order to develop treatments to fine-tune TOR activity as therapies for human diseases. Much less is known about the TOR signaling network in the other major eukaryotic lineage, plants. This project uses a combination of genetic, biochemical, genomic, and proteomic approaches to pursue my recent groundbreaking discovery of an amino acid sensor that activates TOR in plant cells. No amino acid sensors have been previously characterized in plants, although amino acids are the primary form of nitrogen found in many natural soils, and amino acids are the primary transported form of nitrogen between organs in most plant species. Understanding how plants sense and respond to nitrogen is a top priority for plant molecular biologists, because global crop yields rely massively on heavy use of environmentally-harmful and expensive petrochemical fertilizers. This proposed investigation of a nitrogen sensor that activates TOR will enable intelligent breeding efforts to produce crops that are able to generate high crop yields in low nitrogen environments by modulating plants' nitrogen sensing mechanisms. The first specific aim of this project is to first determine how nitrogen sources affect TOR activity, and then to confirm that the proposed amino acid sensor, an aminoacyl tRNA synthetase, does act upstream of TOR signaling. The second aim of this project is to use powerful contemporary proteomic techniques to identify proteins that interact with TOR and/or the proposed nitrogen sensor to control nitrogen-mediated TOR activation using powerful proteomic techniques. Finally, the role of the proposed nitrogen sensor in plant development, crop yields, and responses to environmental nitrogen sources will be explored in several of the most important global crop species. With this innovative approach to exploring how amino acid sensing mechanisms have evolved with TOR signaling in eukaryotes, this project will simultaneously advance understanding of how plants coordinate growth and development with nitrogen availability, and provide original insights into amino acid-TOR networks that will benefit biomedical studies of TOR cell biology in humans.