York Biomedical Research Institute and Department of Biology, University of York, York, UK.
Department of Physics, University of York, York YO10 5DD, UK.
J Cell Sci. 2021 Jan 25;134(2):jcs257733. doi: 10.1242/jcs.257733.
Eukaryotic cells adapt their metabolism to the extracellular environment. Downregulation of surface cargo proteins in response to nutrient stress reduces the burden of anabolic processes whilst elevating catabolic production in the lysosome. We show that glucose starvation in yeast triggers a transcriptional response that increases internalisation from the plasma membrane. Nuclear export of the Mig1 transcriptional repressor in response to glucose starvation increases levels of the Yap1801 and Yap1802 clathrin adaptors, which is sufficient to increase cargo internalisation. Beyond this, we show that glucose starvation results in Mig1-independent transcriptional upregulation of various eisosomal factors. These factors serve to sequester a portion of nutrient transporters at existing eisosomes, through the presence of Ygr130c and biochemical and biophysical changes in Pil1, allowing cells to persist throughout the starvation period and maximise nutrient uptake upon return to replete conditions. This provides a physiological benefit for cells to rapidly recover from glucose starvation. Collectively, this remodelling of the surface protein landscape during glucose starvation calibrates metabolism to available nutrients.This article has an associated First Person interview with the first author of the paper.
真核细胞会根据细胞外环境来调整自身的代谢。当受到营养压力时，细胞会下调表面货物蛋白的表达，减少合成代谢过程的负担，同时提高溶酶体中的分解代谢产物产量。我们发现，酵母在受到葡萄糖饥饿时会触发一个转录反应，从而增加从质膜内化的物质。Mig1 转录阻遏物对葡萄糖饥饿的核输出增加了 yap1801 和 yap1802 网格蛋白接头的水平，这足以增加货物内化。除此之外，我们还发现，葡萄糖饥饿会导致各种内体相关因子的 Mig1 非依赖性转录上调。这些因子通过 Ygr130c 的存在和 Pil1 的生化和生物物理变化，将一部分营养转运蛋白隔离在内体中，使细胞能够在饥饿期间存活，并在回到营养充足的条件下最大限度地吸收营养。这为细胞从葡萄糖饥饿中快速恢复提供了生理上的好处。总的来说，在葡萄糖饥饿期间，对表面蛋白景观的这种重塑使代谢适应可用的营养物质。本文有一篇与该论文第一作者的相关第一人称采访。
