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到浓度的强烈调控。 它们输送的营养物质和细胞的新陈代谢状态。高营养素的存在 浓度会导致相应转运蛋白的迅速内吞和降解。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，代谢压力，如葡萄糖或氨基酸 饥饿还会触发运输器的快速周转，在这种情况下是为了安全的能量和恢复 蛋白质降解所产生的氨基酸。这个项目的重点是监管系统，在一定程度上 决定酵母转运体的周转率：Eisosome和质子泵Pma1。这个 大多数质子驱动的营养转运蛋白定位于质膜结构，称为 等位体。我们的数据表明，Eisosome在其中起储藏隔间的作用 转运体处于非活动状态。Eisosome的存储容量似乎是 由Pma1的活性调节，Pma1是一种质子泵，使用ATP来维持质子梯度 穿过质膜。高Pma1活性导致质子驱动的 转运体的转运体，这反过来导致这些蛋白质的快速周转。这 监管系统确保了质子转运和质子流入之间的平衡 按Pma1导出。我们的研究将集中在这种Eisosome调节的机制以及如何 细胞的新陈代谢状态可以调节这个系统。