The Claudin Family Protein FigA Mediates Ca(2+) Homeostasis in Response to Extracellular Stimuli in Aspergillus nidulans and Aspergillus fumigatus.

The Claudin Family Protein FigA Mediates Ca(2+) Homeostasis in Response to Extracellular Stimuli in Aspergillus nidulans and Aspergillus fumigatus.
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Claudin 家族蛋白 FigA 介导构巢曲霉和烟曲霉响应细胞外刺激的 Ca2 稳态

DOI:
10.3389/fmicb.2018.00977
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发表时间:
2018
影响因子:
5.2
通讯作者:
Lu L
Lu L
中科院分区:
生物学2区
文献类型:
--
作者:
Qian H;Chen Q;Zhang S;Lu L

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Claudin家族蛋白Fig1是一种独特的真菌蛋白,参与酿酒酵母和白色念珠菌交配过程中信息素诱导的钙内流和膜融合。图1是否以及如何调节钙离子稳态以响应细胞外刺激还知之甚少。此前,我们发现酿酒酵母中与图1同源的Nidulans figa类似于高亲和力的钙吸收系统,是在低钙最低限度的培养基中正常生长所必需的。在这项研究中,我们使用钙敏感的光蛋白aequorin来监测活细胞内的胞内游离钙浓度([Ca~(2+)]_c),我们发现,Figa功能障碍降低了高细胞外钙应激诱导的瞬时[Ca~(2+)]_c。此外,FigA与CCHA(一种高亲和力的钙通道)协同作用,协调胞内钙内流,以响应细胞外钙刺激。此外,在细胞外钙存在或不存在的情况下,FigA介导内质网应激诱导的瞬时[Ca~(2+)]_c。最重要的是,这些由FigA介导的[Ca~(2+)]_c反应与其保守的claudin超家族基序密切相关,该基序也是丝状拟青霉菌丝生长和无性发育所必需的。最后对无花果在人体最常见的空气传播真菌烟曲霉中的作用进行了研究。结果表明,Nidulans和Aumigatus中的两个无性同源蛋白不仅在无性发育方面有很大的同源性,而且在调节瞬时[Ca~(2+)]_c方面也有很大程度的同源性。我们的研究拓展了Claudin家族蛋白FigA对细胞外刺激响应钙稳态的认识。
The claudin family protein Fig1 is a unique fungal protein that is involved in pheromone-induced calcium influx and membrane fusion during the mating of Saccharomyces cerevisiae and Candida albicans. Whether and how Fig1 regulates Ca2+ homeostasis in response to extracellular stimuli is poorly understood. Previously, we found Aspergillus nidulans FigA, a homolog of Fig1 in S. cerevisiae, similar to the high-affinity calcium uptake system, is required for normal growth under low-Ca2+ minimal medium. In this study, using the calcium-sensitive photoprotein aequorin to monitor cytosolic free calcium concentration ([Ca2+]c) in living cells, we found that the FigA dysfunction decreases the transient [Ca2+]c induced by a high extracellular calcium stress. Furthermore, FigA acts synergistically with CchA (a high-affinity Ca2+ channel) to coordinate cytoplasmic Ca2+ influx in response to an extracellular Ca2+ stimulus. Moreover, FigA mediates ER stress-induced transient [Ca2+]c in the presence or absence of extracellular calcium. Most importantly, these [Ca2+]c responses mediated by FigA are closely related to its conserved claudin superfamily motif, which is also required for hyphal growth and asexual development in A. nidulans. Finally, the function of FigA in Aspergillus fumigatus, the most common airborne human fungal pathogen was studied. The result showed that the two FigA homologous in A. nidulans and A. fumigatus have a large degree of functional homology not only in asexual development but also in regulating transient [Ca2+]c. Our study expands the knowledge of claudin family protein FigA in Ca2+ homeostasis in response to extracellular stimuli.
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