Cyclic AMP Pathway Activation and Extracellular Zinc Induce Rapid Intracellular Zinc Mobilization in Candida albicans
Cyclic AMP Pathway Activation and Extracellular Zinc Induce Rapid Intracellular Zinc Mobilization in Candida albicans
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白色念珠菌中环 AMP 途径激活和细胞外锌诱导细胞内锌快速动员
DOI：
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发表时间：
2018
影响因子：
5.2
通讯作者：
A. Fuglsang
中科院分区：
文献类型：
--
作者：
L. Kjellerup;A. M. Winther;Duncan W. Wilson;A. Fuglsang
锌是一种必需的微量营养素，是一系列锌依赖酶和转录因子所必需的。在哺乳动物细胞中，锌作为第二信使分子。然而，锌在真菌王国中信号传导的作用尚未确定。在这里，我们使用细胞内锌报告细胞，锌-5，它可以可视化锌在白色念珠菌内质网和其他内部膜系统的组成部分。我们为这种主要的人类真菌病原体的环AMP/PKA-和锌信号传导之间的联系提供了证据。葡萄糖刺激会触发这种真菌的环状AMP峰值，导致细胞内锌的快速动员，这种“锌通量”可以用磷酸二酯酶抑制剂刺激，并通过抑制腺苷酸环化酶或PKA来阻断。细胞外锌刺激细胞也会产生类似的细胞内锌的动员，这种作用可以通过螯合剂EDTA逆转。然而，锌诱导的锌通量与环AMP无关。总之，我们发现激活环AMP/PKA通路会触发真菌细胞内锌的动员。据我们所知，这是人类真菌病原体中首次描述的环AMP信号与锌稳态之间的联系。
Zinc is an essential micronutrient, required for a range of zinc-dependent enzymes and transcription factors. In mammalian cells, zinc serves as a second messenger molecule. However, a role for zinc in signaling has not yet been established in the fungal kingdom. Here, we used the intracellular zinc reporter, zinbo-5, which allowed visualization of zinc in the endoplasmic reticulum and other components of the internal membrane system in Candida albicans. We provide evidence for a link between cyclic AMP/PKA- and zinc-signaling in this major human fungal pathogen. Glucose stimulation, which triggers a cyclic AMP spike in this fungus resulted in rapid intracellular zinc mobilization and this “zinc flux” could be stimulated with phosphodiesterase inhibitors and blocked via inhibition of adenylate cyclase or PKA. A similar mobilization of intracellular zinc was generated by stimulation of cells with extracellular zinc and this effect could be reversed with the chelator EDTA. However, zinc-induced zinc flux was found to be cyclic AMP independent. In summary, we show that activation of the cyclic AMP/PKA pathway triggers intracellular zinc mobilization in a fungus. To our knowledge, this is the first described link between cyclic AMP signaling and zinc homeostasis in a human fungal pathogen.
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影响因子：
4
作者：
Bozym, Rebecca A.;Thompson, Richard B.;Fierke, Carol A.
通讯作者：
Fierke, Carol A.
宿主和真菌通过锌透镜的交叉点。
影响因子：
5.4
作者：
Wilson,Duncan;DeepeJr,GeorgeS
通讯作者：
DeepeJr,GeorgeS
DOI：
10.1016/j.bbamcr.2012.04.001
发表时间：
2012-09
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Dean KM;Qin Y;Palmer AE
通讯作者：
Palmer AE
影响因子：
3.9
作者：
Wilson, Stevin;Bird, Amanda J.
通讯作者：
Bird, Amanda J.
影响因子：
--
作者：
KONING, AJ;LUM, PY;WRIGHT, R
通讯作者：
WRIGHT, R