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: 9353887
• 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/9353887
• 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 Plant; 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; 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：真核增长受TOR的调节，Tor是一种激活的激酶 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失调导致或导致包括癌症在内的一系列人类疾病 肥胖，病毒感染，糖尿病，衰老和神经退行性。 TOR信号传导很强 酵母和动物细胞生物学家之间的研究，他们试图表征 控制TOR信号网络，以开发作为疗法的治疗方法 对于人类疾病。关于另一个主要专业的TOR信号网络知之甚少 真核生物谱系，植物。该项目结合了遗传，生化，基因组和 蛋白质组学的方法来追求我最近对氨基酸传感器的开创性发现 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， 尽管氨基酸是在许多天然土壤和氨基酸中发现的氮的主要形式 是大多数植物物种中器官之间的主要运输形式。理解 植物如何感知和对氮的反应是植物分子生物学家的重点，因为 全球作物的产量极大地依赖于大量使用环保和昂贵的 石化肥料。这项提出的对激活TOR的氮传感器的研究将会 实现智能育种努力，以生产能够以低作物产生高产的农作物 氮环境通过调节植物的氮感应机制。第一个具体目的的 该项目首先确定氮源如何影响TOR活动，然后确认 提出的氨基酸传感器是一种氨基酰基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蛋白质 使用强大的蛋白质组学技术激活。最后，提出的氮传感器的作用 在植物开发中，将探索农作物的产量和对环境氮源的反应 在最重要的全球作物中。采用这种创新的方法来探索如何 氨基酸传感机制已随着真核生物的TOR信号的发展而发展，该项目将 同时提高对植物如何协调生长和发展的理解 氮的可用性，并提供对氨基酸托网络的原始见解，这些网络将受益 人类Tor细胞生物学的生物医学研究。