Regulation of nutrient transporters

营养转运蛋白的调节

• 批准号: 9291233
• 负责人: MARKUS BABST
• 金额: $ 36.11万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9291233
• 关键词: Acute; Adenomatous Polyposis Coli Protein; Affect; Amino Acids; Carrier Proteins; Caveolae; Cell membrane; Cell physiology; Cells; Controlled Study; Data; Diabetes Mellitus; Drops; Endocytosis; Ensure; Environment; Equilibrium; Eukaryota; Excision; Feedback; Glucose; Goals; Growth; Link; Lipids; Malignant Neoplasms; Mammalian Cell; Mediating; Membrane; Metabolic; Metabolic Pathway; Metabolic stress; Metabolism; Mitochondria; Nutrient; Pathologic; Phosphorylation; Phosphotransferases; Physiological; Play; Post-Translational Regulation; Production; Proteins; Proton Pump; Protons; Pump; Recruitment Activity; Regulation; Role; Starvation; Surface; System; Testing; Transcriptional Regulation; Ubiquitination; Yeasts; extracellular; insight; protein degradation; uptake

Project Summary The surface expression of nutrient transporters is acutely regulated by the concentration of the nutrient they pump and the metabolic state of the cell. The presence of high nutrient concentrations causes rapid endocytosis and degradation of the corresponding transporter. This negative-feedback system ensures that cytoplasmic nutrient concentration remains in a physiological range. On the other hand, metabolic stress such as glucose or amino acid starvation also triggers rapid turnover of transporters, in this case to safe energy and recover amino acids by protein degradation. This project focuses on a regulatory system that in part determines the turnover rate of yeast transporters: eisosomes and the proton pump Pma1. The majority of proton-driven nutrient transporters localize to plasma membrane structures called eisosomes. Our data suggest that eisosomes function as storage compartments in which transporters are kept in an inactive state. The storage capacity of eisosomes seems to be regulated by the activity of Pma1, a proton pump that uses ATP to maintain the proton gradient across the plasma membrane. High Pma1 activity causes the release of proton-driven transporters from eisosomes, which in turn results in rapid turnover of these proteins. This regulatory system ensures a balance between the proton influx by transporters and proton export by Pma1. Our studies will focus on the mechanism of this eisosome regulation and how the metabolic state of the cell can modulate this system.

项目摘要 营养转运蛋白的表面表达受蛋白质浓度的剧烈调节。 他们泵的营养和细胞的代谢状态。高营养物质的存在 浓度引起相应转运蛋白的快速内吞和降解。这 负反馈系统确保细胞质营养浓度保持在 生理范围。另一方面，代谢应激如葡萄糖或氨基酸 饥饿还引发了运输者的快速更替，在这种情况下， 蛋白质降解产生的氨基酸。该项目的重点是一个监管制度， 决定酵母转运蛋白的周转率：eisosomes和质子泵Pma1。的 大多数质子驱动的营养转运蛋白定位于质膜结构，称为 异质体我们的数据表明，eisosomes功能作为存储隔间，其中 传输器保持在非活动状态。Eisosomes的储存能力似乎是 由Pma1的活性调节，Pma1是一种质子泵，使用ATP维持质子梯度 穿过细胞膜高Pma1活性导致质子驱动的 这反过来又导致这些蛋白质的快速周转。这 调节系统确保通过转运蛋白的质子流入和质子转运之间的平衡。 通过Pma1输出。我们的研究将集中在这种Eisosome调节的机制，以及如何 细胞的代谢状态可以调节该系统。