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TORC1 和 PKA 的核糖体生物发生活性与出芽酵母细胞周期同步振荡。

TORC1 and PKA activity towards ribosome biogenesis oscillates in synchrony with the budding yeast cell cycle.

机构信息

Molecular Systems Biology, Groningen Biomolecular Sciences & Biotechnology Institute, University of Groningen, 9747 AG Groningen, The Netherlands.

出版信息

J Cell Sci. 2022 Sep 15;135(18). doi: 10.1242/jcs.260378. Epub 2022 Sep 28.

Abstract

Recent studies have revealed that the growth rate of budding yeast and mammalian cells varies during the cell cycle. By linking a multitude of signals to cell growth, the highly conserved target of rapamycin complex 1 (TORC1) and protein kinase A (PKA) pathways are prime candidates for mediating the dynamic coupling between growth and division. However, measurements of TORC1 and PKA activity during the cell cycle are still lacking. By following the localization dynamics of two TORC1 and PKA targets via time-lapse microscopy in hundreds of yeast (Saccharomyces cerevisiae) cells, we found that the activity of these pathways towards ribosome biogenesis fluctuates in synchrony with the cell cycle even under constant external conditions. Analysis of the effects of mutations of upstream TORC1 and PKA regulators suggests that internal metabolic signals partially mediate these activity changes. Our study reveals a new aspect of TORC1 and PKA signaling, which will be important for understanding growth regulation during the cell cycle.

摘要

最近的研究表明,芽殖酵母和哺乳动物细胞的生长速率在细胞周期中会发生变化。高度保守的雷帕霉素靶蛋白复合物 1(TORC1)和蛋白激酶 A(PKA)途径通过将多种信号与细胞生长联系起来,是介导生长和分裂之间动态耦联的主要候选途径。然而,在细胞周期中测量 TORC1 和 PKA 的活性仍然缺乏。通过在数百个酵母(酿酒酵母)细胞中通过延时显微镜观察两个 TORC1 和 PKA 靶标的定位动态,我们发现,即使在外部条件不变的情况下,这些途径对核糖体生物发生的活性也会与细胞周期同步波动。对 TORC1 和 PKA 上游调节剂突变的影响的分析表明,内部代谢信号部分介导了这些活性变化。我们的研究揭示了 TORC1 和 PKA 信号的一个新方面,这对于理解细胞周期中的生长调控将是重要的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92f9/9658999/0944ba5fdeb4/joces-135-260378-g1.jpg

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