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

项目概述：真核细胞生长受TOR调节，TOR是一种由氨基激活的激酶， 酸和葡萄糖，然后广泛促进抗氧化剂，包括蛋白质，脂质和核苷酸 合成. TOR失调导致或促成一系列人类疾病，包括癌症， 肥胖、病毒感染、糖尿病、衰老和神经变性。TOR信号传导处于强烈的 酵母和动物细胞生物学家之间的调查，谁寻求表征的机制， 控制TOR信号网络，以开发治疗方法来微调TOR活性作为治疗方法 for human人类diseases疾病.在另一个主要领域，对TOR信令网络的了解要少得多。 真核生物谱系，植物。该项目使用遗传学、生物化学、基因组学和 蛋白质组学的方法来追求我最近的突破性发现的氨基酸传感器， 激活植物细胞中的TOR以前没有在植物中表征氨基酸传感器， 虽然氨基酸是在许多天然土壤中发现的氮的主要形式， 是大多数植物器官间氮素运输的主要形式。理解 植物如何感知和响应氮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 石化肥料这项关于激活TOR的氮传感器的研究将 使智能育种工作，以生产能够产生高作物产量的作物， 氮环境的影响。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，氨酰tRNA合成酶，确实在TOR信号传导的上游起作用。 该项目的第二个目的是使用强大的当代蛋白质组学技术来识别 与TOR和/或所提出的氮传感器相互作用以控制氮介导的 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，作物产量，以及对环境氮源的反应将进行探讨 在几种最重要的全球性作物中。通过这种创新的方法来探索 氨基酸传感机制已经随着真核生物中的TOR信号而进化，该项目将 同时促进了解植物如何协调生长和发展， 氮的可用性，并提供对氨基酸-TOR网络的原始见解， 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.