利用基于群体和单细胞的方法探索 Snf1/Mig1 网络中与碳源相关的定位和磷酸化。

IF 4.1 3区 生物学 Q2 CELL BIOLOGY Microbial Cell Pub Date : 2024-05-16 eCollection Date: 2024-01-01 DOI:10.15698/mic2024.05.822
Svenja Braam, Farida Tripodi, Linnea Österberg, Sebastian Persson, Niek Welkenhuysen, Paola Coccetti, Marija Cvijovic
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引用次数: 0

摘要

AMPK/SNF1 通路控制着真核细胞的能量平衡,特别是影响葡萄糖的去抑制作用。在 S. cerevisiae 中,Snf1 被磷酸化,从而在葡萄糖耗竭时被激活。这种激活是必要的,但不足以介导葡萄糖去抑制,这表明还有其他葡萄糖依赖性调节机制。利用光漂白后荧光恢复(FRAP)和非线性混合效应模型,我们探索了 Snf1 的空间动态以及 Snf1 磷酸化与其目标 Mig1 之间受六糖控制的关系。我们的结果表明,Snf1的失活调节了Mig1的定位,而Snf1定位到细胞核的动力学受非发酵性碳源存在的调节。我们的数据让我们深入了解了这一中心信号通路在协调细胞对波动环境线索的反应方面的真正复杂性。这些见解不仅拓展了我们对葡萄糖稳态的理解,还为进一步研究评估 Snf1 定位与其磷酸化状态和下游靶标调控的重要性铺平了道路。
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Exploring carbon source related localization and phosphorylation in the Snf1/Mig1 network using population and single cell-based approaches.

The AMPK/SNF1 pathway governs energy balance in eukaryotic cells, notably influencing glucose de-repression. In S. cerevisiae, Snf1 is phosphorylated and hence activated upon glucose depletion. This activation is required but is not sufficient for mediating glucose de-repression, indicating further glucose-dependent regulation mechanisms. Employing fluorescence recovery after photobleaching (FRAP) in conjunction with non-linear mixed effects modelling, we explore the spatial dynamics of Snf1 as well as the relationship between Snf1 phosphorylation and its target Mig1 controlled by hexose sugars. Our results suggest that inactivation of Snf1 modulates Mig1 localization and that the kinetic of Snf1 localization to the nucleus is modulated by the presence of non-fermentable carbon sources. Our data offer insight into the true complexity of regulation of this central signaling pathway in orchestrating cellular responses to fluctuating environmental cues. These insights not only expand our understanding of glucose homeostasis but also pave the way for further studies evaluating the importance of Snf1 localization in relation to its phosphorylation state and regulation of downstream targets.

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来源期刊
Microbial Cell
Microbial Cell Multiple-
CiteScore
6.40
自引率
0.00%
发文量
32
审稿时长
12 weeks
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