Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, China
Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, China.
mBio. 2019 Jan 15;10(1):e02320-18. doi: 10.1128/mBio.02320-18.
is the most common cause of invasive fungal infections in humans. Its ability to sense and adapt to changing carbon dioxide levels is crucial for its pathogenesis. Carbon dioxide promotes hyphal development. The hypha-specific transcription factor Ume6 is rapidly degraded in air, but is stable under physiological CO and hypoxia to sustain hyphal elongation. Here, we show that Ume6 stability is regulated by two parallel E3 ubiquitin ligases, SCF and Ubr1, in response to CO and O, respectively. To uncover the CO signaling pathway that regulates Ume6 stability, we performed genetic screens for mutants unable to respond to CO for sustained filamentation. We find that the type 2C protein phosphatase Ptc2 is specifically required for CO-induced stabilization of Ume6 and hyphal elongation. In contrast, the cyclin-dependent kinase Ssn3 is found to be required for Ume6 phosphorylation and degradation in atmospheric CO Furthermore, we find that Ssn3 is dephosphorylated in 5% CO in a Ptc2-dependent manner, whereas deletion of has no effect on Ssn3 phosphorylation in air. Our study uncovers the Ptc2-Ssn3 axis as a new CO signaling pathway that controls hyphal elongation by regulating Ume6 stability in The capacity to sense and adapt to changing carbon dioxide levels is crucial for all organisms. In fungi, CO is a key determinant involved in fundamental biological processes, including growth, morphology, and virulence. In the pathogenic fungus , high CO is directly sensed by adenylyl cyclase to promote hyphal growth. However, little is known about the mechanism by which hyphal development is maintained in response to physiological levels of CO Here we report that a signal transduction system mediated by a phosphatase-kinase pair controls CO-responsive Ume6 phosphorylation and stability that in turn dictate hyphal elongation. Our results unravel a new regulatory mechanism of CO signaling in fungi.
是人类中最常见的侵袭性真菌感染的原因。它感应和适应不断变化的二氧化碳水平的能力对其发病机制至关重要。二氧化碳促进菌丝发育。菌丝特异性转录因子 Ume6 在空气中迅速降解，但在生理 CO 和缺氧下稳定，以维持菌丝伸长。在这里，我们表明 Ume6 的稳定性受两个平行的 E3 泛素连接酶 SCF 和 Ubr1 调节，分别响应 CO 和 O。为了揭示调节 Ume6 稳定性的 CO 信号通路，我们进行了遗传筛选，以寻找无法对 CO 持续进行丝状反应的突变体。我们发现，2C 型蛋白磷酸酶 Ptc2 是 CO 诱导 Ume6 稳定和菌丝伸长所特需的。相比之下，发现细胞周期蛋白依赖性激酶 Ssn3 是 Ume6 在大气 CO 中的磷酸化和降解所必需的。此外，我们发现 Ptc2 依赖性地在 5% CO 中 Ssn3 去磷酸化，而缺失 对 Ssn3 在空气中的磷酸化没有影响。我们的研究揭示了 Ptc2-Ssn3 轴作为一种新的 CO 信号通路，通过调节 Ume6 的稳定性来控制菌丝伸长，在真菌中，CO 是参与包括生长、形态和毒力在内的基本生物学过程的关键决定因素。在致病真菌中，高浓度的 CO 直接被腺苷酸环化酶感应，以促进菌丝生长。然而，对于菌丝发育如何在生理浓度的 CO 下维持，人们知之甚少。在这里，我们报告了一个由磷酸酶-激酶对介导的信号转导系统控制 CO 响应性 Ume6 的磷酸化和稳定性，从而决定菌丝伸长。我们的结果揭示了真菌中 CO 信号的新调节机制。
