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Regulation of nutrient transporters

营养转运蛋白的调节

基本信息

批准号：
9978900
负责人：
MARKUS BABST
金额：
$ 36.35万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-01 至 2021-12-31
项目状态：
已结题

项目摘要

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.

项目概要营养转运蛋白的表面表达受到营养转运蛋白浓度的强烈调节。它们泵送的营养物质和细胞的代谢状态。高营养成分的存在浓度导致相应转运蛋白的快速内吞作用和降解。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会引发运输者的快速周转，在这种情况下是为了安全能源和恢复蛋白质降解产生的氨基酸。该项目的重点是监管系统，该系统部分地决定酵母转运蛋白的周转率：eisosomes 和质子泵 Pma1。这大多数质子驱动的营养转运蛋白定位于质膜结构，称为异构体。我们的数据表明，eisosomes 起到存储隔间的作用，其中运输机保持在非活动状态。 eisosomes 的存储容量似乎是受 Pma1 活性调节，Pma1 是一种使用 ATP 维持质子梯度的质子泵穿过质膜。高 Pma1 活性导致质子驱动的释放来自 eisosomes 的转运蛋白，这反过来又导致这些蛋白质的快速周转。这监管系统确保转运蛋白流入的质子与质子之间的平衡通过 Pma1 导出。我们的研究将集中于这种内切体调节的机制以及如何细胞的代谢状态可以调节该系统。