共查询到20条相似文献,搜索用时 31 毫秒
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In the human fungal pathogen Candida albicans, environmental pH has profound effects on morphogenesis and response to extracellular pH is clearly relevant to the pathogenicity of this fungus. Yeast cells have evolved a complex network of mechanisms in response to the environmental pH and they often require the integration of the Rim101 and calcineurin/Crz1 signaling pathways. Ca(2+) burst is a common cellular response when cells are exposed to environmental stresses; therefore, in this study, we asked whether it follows the same case under alkaline stress and whether this calcium change is regulated by Rim101p and Crz1p. We confirmed the calcium influx was activated by KOH stimuli using a flow cytometry-based method, but it was obviously abolished in cells lacking MID1 or CCH1. We also found that alkaline pH-induced activation of the PHO89 promoter was blocked without the same gene; moreover, the response was Crz1p- and Rim101p-dependent. Finally, we investigated the regulation role of Rim101p and Crz1p in calcium influx through MID1, CCH1 and YVC1 genes, which were all downregulated in rim101Δ/Δ and crz1Δ/Δ mutants. The important role of calcium influx in the alkaline stress response and its regulation suggested a potential integration effect of Rim101 and Crz1 signaling pathways in C. albicans. 相似文献
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Ying-Lien Chen Shang-Jie Yu Hsin-Yu Huang Ya-Lin Chang Virginia N. Lehman Fitz Gerald S. Silao Ursela G. Bigol Alice Alma C. Bungay Anna Averette Joseph Heitman 《Eukaryotic cell》2014,13(7):844-854
Candida tropicalis, a species closely related to Candida albicans, is an emerging fungal pathogen associated with high mortality rates of 40 to 70%. Like C. albicans and Candida dubliniensis, C. tropicalis is able to form germ tubes, pseudohyphae, and hyphae, but the genes involved in hyphal growth machinery and virulence remain unclear in C. tropicalis. Recently, echinocandin- and azole-resistant C. tropicalis isolates have frequently been isolated from various patients around the world, making treatment difficult. However, studies of the C. tropicalis genes involved in drug tolerance are limited. Here, we investigated the roles of calcineurin and its potential target, Crz1, for core stress responses and pathogenesis in C. tropicalis. We demonstrate that calcineurin and Crz1 are required for hyphal growth, micafungin tolerance, and virulence in a murine systemic infection model, while calcineurin but not Crz1 is essential for tolerance of azoles, caspofungin, anidulafungin, and cell wall-perturbing agents, suggesting that calcineurin has both Crz1-dependent and -independent functions in C. tropicalis. In addition, we found that calcineurin and Crz1 have opposite roles in controlling calcium tolerance. Calcineurin serves as a negative regulator, while Crz1 plays a positive role for calcium tolerance in C. tropicalis. 相似文献
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Mutual independence of alkaline‐ and calcium‐mediated signalling in Aspergillus fumigatus refutes the existence of a conserved druggable signalling nexus
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Omar Loss Margherita Bertuzzi Yu Yan Natalie Fedorova Bethany L. McCann Darius Armstrong‐James Eduardo A. Espeso Nick D. Read William C. Nierman Elaine M. Bignell 《Molecular microbiology》2017,106(6):861-875
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Good fungi gone bad: the corruption of calcineurin 总被引:17,自引:0,他引:17
Fox DS Heitman J 《BioEssays : news and reviews in molecular, cellular and developmental biology》2002,24(10):894-903
Calcineurin is a Ca(2+)/calmodulin-activated protein phosphatase that is conserved in eukaryotes, from yeast to humans, and is the conserved target of the immunosuppressive drugs cyclosporin A (CsA) and FK506. Genetic studies in yeast and fungi established the molecular basis of calcineurin inhibition by the cyclophilin A-CsA and FKBP12-FK506 complexes. Calcineurin also functions in fungi to control a myriad of physiological processes including cell cycle progression, cation homeostasis, and morphogenesis. Recent investigations into the molecular mechanisms of pathogenesis in Candida albicans and Cryptococcus neoformans, two fungi that cause life-threatening infections in humans, have revealed an essential role for calcineurin in morphogenesis, virulence, and antifungal drug action. Novel non-immunosuppressive analogs of the calcineurin inhibitors CsA and FK506 that retain antifungal activity have been identified and hold promise as candidate antifungal drugs. In addition, comparisons of calcineurin function in both fungi and humans may identify fungal-specific components of calcineurin-signaling pathways that could be targeted for therapy, as well as conserved elements of calcium signaling events. 相似文献
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The target of rapamycin (TOR) kinase is a conserved regulator of cell growth and functions within 2 different protein complexes, TORC1 and TORC2, where TORC2 positively controls macroautophagy/autophagy during amino acid starvation. Under these conditions, TORC2 signaling inhibits the activity of the calcium-regulated phosphatase calcineurin and promotes the general amino acid control (GAAC) response and autophagy. Here we demonstrate that TORC2 regulates calcineurin by controlling the respiratory activity of mitochondria. In particular, we find that mitochondrial oxidative stress affects the calcium channel regulatory protein Mid1, which we show is an essential upstream activator of calcineurin. Thus, these findings describe a novel regulation for autophagy that involves TORC2 signaling, mitochondrial respiration, and calcium homeostasis. 相似文献