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黄曲霉典型G蛋白偶联受体的全球调查。

Global survey of canonical Aspergillus flavus G protein-coupled receptors.

作者信息

Affeldt Katharyn J, Carrig Joseph, Amare Meareg, Keller Nancy P

机构信息

Department of Medical Microbiology & Immunology, University of Wisconsin-Madison, Madison, Wisconsin, USA.

Department of Bacteriology, University of Wisconsin-Madison, Madison, Wisconsin, USA.

出版信息

mBio. 2014 Oct 14;5(5):e01501-14. doi: 10.1128/mBio.01501-14.

Abstract

G protein-coupled receptors (GPCRs) are transmembrane receptors that relay signals from the external environment inside the cell, allowing an organism to adapt to its surroundings. They are known to detect a vast array of ligands, including sugars, amino acids, pheromone peptides, nitrogen sources, oxylipins, and light. Despite their prevalence in fungal genomes, very little is known about the functions of filamentous fungal GPCRs. Here we present the first full-genome assessment of fungal GPCRs through characterization of null mutants of all 15 GPCRs encoded by the aflatoxin-producing fungus Aspergillus flavus. All strains were assessed for growth, development, ability to produce aflatoxin, and response to carbon sources, nitrogen sources, stress agents, and lipids. Most GPCR mutants were aberrant in one or more response processes, possibly indicative of cross talk in downstream signaling pathways. Interestingly, the biological defects of the mutants did not correspond with assignment to established GPCR classes; this is likely due to the paucity of data for characterized fungal GPCRs. Many of the GPCR transcripts were differentially regulated under various conditions as well. The data presented here provide an extensive overview of the full set of GPCRs encoded by A. flavus and provide a framework for analysis in other fungal species. Importance: Aspergillus flavus is an opportunistic pathogen of crops and animals, including humans, and it produces a carcinogenic toxin called aflatoxin. Because of this, A. flavus accounts for food shortages and economic losses in addition to sickness and death. Effective means of combating this pathogen are needed to mitigate its deleterious effects. G protein-coupled receptors (GPCRs) are often used as therapeutic targets due to their signal specificity, and it is estimated that half of all drugs target GPCRs. In fungi such as A. flavus, GPCRs are likely necessary for sensing the changes in the environment, including food sources, developmental signals, stress agents, and signals from other organisms. Therefore, elucidating their functions in A. flavus could identify ideal receptors against which to develop antagonists.

摘要

G蛋白偶联受体(GPCRs)是跨膜受体,可将细胞外部环境中的信号传递到细胞内部,使生物体能够适应周围环境。已知它们能检测各种各样的配体,包括糖类、氨基酸、信息素肽、氮源、氧化脂质和光。尽管它们在真菌基因组中普遍存在,但关于丝状真菌GPCRs的功能却知之甚少。在此,我们通过对产黄曲霉毒素的黄曲霉所编码的15种GPCRs的缺失突变体进行表征,首次对真菌GPCRs进行了全基因组评估。对所有菌株的生长、发育、产黄曲霉毒素的能力以及对碳源、氮源、应激因子和脂质的反应进行了评估。大多数GPCR突变体在一个或多个反应过程中表现异常,这可能表明下游信号通路中存在相互作用。有趣的是,突变体的生物学缺陷与已确定的GPCR类别并不对应;这可能是由于已表征的真菌GPCRs的数据匮乏所致。许多GPCR转录本在各种条件下也受到差异调节。本文提供的数据全面概述了黄曲霉所编码的全套GPCRs,并为其他真菌物种的分析提供了框架。重要性:黄曲霉是包括人类在内的农作物和动物的机会性病原体,它会产生一种致癌毒素——黄曲霉毒素。因此,除了疾病和死亡外,黄曲霉还导致粮食短缺和经济损失。需要有效的方法来对抗这种病原体,以减轻其有害影响。G蛋白偶联受体(GPCRs)由于其信号特异性,常被用作治疗靶点,据估计,所有药物中有一半靶向GPCRs。在黄曲霉等真菌中,GPCRs可能是感知环境变化所必需的,这些变化包括食物来源、发育信号、应激因子以及来自其他生物体的信号。因此,阐明它们在黄曲霉中的功能可以确定开发拮抗剂的理想受体。

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