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

氨酰 tRNA 合成酶是一种氮传感器，可激活植物中的 TOR

• 批准号: 9211977
• 负责人: Jacob O Brunkard
• 金额: $ 31.5万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-16 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9211977
• 关键词: Affect; Aging; Agriculture; Amino Acids; Amino Acyl-tRNA Synthetases; Anabolism; Animals; Asparagine; Biochemical; Biomedical Research; Breeding; Cell division; Cells; Cellular biology; Complex; Development; Diabetes Mellitus; Disease; Disputes; Environment; Eukaryota; Eukaryotic Cell; Evolution; Fertilizers; Functional disorder; Genes; Genetic; Genetic Screening; Genomics; Glucose; Goals; Growth; Growth and Development function; Human; Investigation; Knowledge; Lipids; Location; Malignant Neoplasms; Mediating; Metabolism; Microscopy; Molecular; Mutate; Nerve Degeneration; Nitrogen; Nutrient; Obesity; Organ; Outcome; Phenotype; Phosphotransferases; Physiology; Plants; Plasmodesmata; Problem Solving; Proteins; Proteomics; Role; Signal Transduction; Soil; Source; Techniques; Testing; Translations; Variant; Vascular System; Virus Diseases; Yeasts; human disease; improved; innovation; insight; leucine-tRNA; mutant; novel; nucleotide metabolism; plant growth/development; protein complex; response; sensor; therapy design; trafficking; transcriptomics

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.

项目摘要：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，然后广泛促进合成代谢，包括蛋白质、脂质和核苷酸 合成。 TOR 失调会导致或导致一系列人类疾病，包括癌症、 肥胖、病毒感染、糖尿病、衰老和神经退行性疾病。 TOR 信号传导处于紧张状态 对酵母和动物细胞生物学家进行的调查，他们试图描述其机制 控制 TOR 信号网络，以开发微调 TOR 活性的治疗方法 对于人类疾病。对于其他主要领域的 TOR 信号网络知之甚少 真核谱系，植物。该项目结合了遗传、生化、基因组和 蛋白质组学方法来追求我最近对氨基酸传感器的突破性发现 激活植物细胞中的 TOR。此前尚未在植物中表征过氨基酸传感器， 尽管氨基酸是许多天然土壤中发现的氮的主要形式，并且氨基酸 是大多数植物物种器官之间氮的主要运输形式。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。这项对激活 TOR 的氮传感器的拟议研究将 使智能育种工作能够生产出能够以较低的成本产生高产量的作物 通过调节植物的氮传感机制来实现氮环境。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（一种氨酰 tRNA 合成酶）确实在 TOR 信号传导的上游发挥作用。 该项目的第二个目标是利用强大的当代蛋白质组技术来识别 与 TOR 和/或提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技术激活 TOR。最后，提出的氮气传感器的作用 在植物发育中，将探讨作物产量和对环境氮源的反应 存在于几种最重要的全球农作物品种中。通过这种创新方法来探索如何 氨基酸传感机制随着真核生物中的 TOR 信号传导而进化，该项目将 同时增进对植物如何协调生长和发育的理解 氮的可用性，并提供对氨基酸-TOR网络的原始见解，这将受益 人类 TOR 细胞生物学的生物医学研究。