Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Mol Biol Cell. 2011 Oct;22(19):3671-83. doi: 10.1091/mbc.E11-04-0309. Epub 2011 Aug 10.
Glucose is a rich source of energy and the raw material for biomass increase. Many eukaryotic cells remodel their physiology in the presence and absence of glucose. The yeast Saccharomyces cerevisiae undergoes changes in transcription, translation, metabolism, and cell polarity in response to glucose availability. Upon glucose starvation, translation initiation and cell polarity are immediately inhibited, and then gradually recover. In this paper, we provide evidence that, as in cell polarity and translation, traffic at the trans-Golgi network (TGN) and endosomes is regulated by glucose via an unknown mechanism that depends on protein kinase A (PKA). Upon glucose withdrawal, clathrin adaptors exhibit a biphasic change in localization: they initially delocalize from the membrane within minutes and later partially recover onto membranes. Additionally, the removal of glucose induces changes in posttranslational modifications of adaptors. Ras and Gpr1 signaling pathways, which converge on PKA, are required for changes in adaptor localization and changes in posttranslational modifications. Acute inhibition of PKA demonstrates that inhibition of PKA prior to glucose withdrawal prevents several adaptor responses to starvation. This study demonstrates that PKA activity prior to glucose starvation primes membrane traffic at the TGN and endosomes in response to glucose starvation.
葡萄糖是一种丰富的能量来源，也是生物量增加的原料。许多真核细胞在有或没有葡萄糖的情况下都会重塑其生理机能。酵母酿酒酵母（Saccharomyces cerevisiae）会根据葡萄糖的可用性，在转录、翻译、代谢和细胞极性方面发生变化。在葡萄糖饥饿时，翻译起始和细胞极性会立即受到抑制，然后逐渐恢复。在本文中，我们提供了证据表明，与细胞极性和翻译一样，通过一个未知的、依赖于蛋白激酶 A（PKA）的机制，高尔基体网络（TGN）和内体的运输也受到葡萄糖的调节。葡萄糖耗尽后，网格蛋白衔接蛋白在定位上表现出双相变化：它们最初在几分钟内从膜上脱定位，然后部分恢复到膜上。此外，葡萄糖的去除诱导衔接子的翻译后修饰发生变化。Ras 和 Gpr1 信号通路，它们都汇聚到 PKA，是衔接蛋白定位变化和翻译后修饰变化所必需的。PKA 的急性抑制表明，在葡萄糖饥饿之前抑制 PKA 可以防止几种衔接蛋白对饥饿的反应。本研究表明，在葡萄糖饥饿之前 PKA 的活性可以为对葡萄糖饥饿的 TGN 和内体的膜运输做好准备。
