Distinct roles for the p53-like transcription factor XprG and autophagy genes in the response to starvation

Katz, Margaret; Buckland, Rebecca; Hunter, Cameron C.; Todd, Richard B.

doi:10.1016/j.fgb.2015.08.006

Cited by 10 publications

(7 citation statements)

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“…1b; Additional file 3: Table S2). Two key autophagy genes, NCU00188 and NCU01545, encoding orthologs of ATG1/AtgA and ATG8/AtgH in S. cerevisiae and A. nidulans , respectively [31], showed increased expression levels under the no-carbon condition in comparison with 2.0% glucose treatment (Additional file 2: Table S1), whereas vib - 1 (NCU03725), an ortholog of the crucial autolysis regulator XprG in A. nidulans [32], was dramatically downregulated (Additional file 2: Table S1). These data suggest complex coordination between autophagy and autolysis in N. crassa to cope with carbon starvation as these two processes might be activated independently [32].…”

Section: Resultsmentioning

confidence: 99%

Identification and characterization of the glucose dual-affinity transport system in Neurospora crassa: pleiotropic roles in nutrient transport, signaling, and carbon catabolite repression

Wang

Gao

et al. 2017

Biotechnol Biofuels

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BackgroundThe glucose dual-affinity transport system (low- and high-affinity) is a conserved strategy used by microorganisms to cope with natural fluctuations in nutrient availability in the environment. The glucose-sensing and uptake processes are believed to be tightly associated with cellulase expression regulation in cellulolytic fungi. However, both the identities and functions of the major molecular components of this evolutionarily conserved system in filamentous fungi remain elusive. Here, we systematically identified and characterized the components of the glucose dual-affinity transport system in the model fungus Neurospora crassa.ResultsUsing RNA sequencing coupled with functional transport analyses, we assigned GLT-1 (K m = 18.42 ± 3.38 mM) and HGT-1/-2 (K m = 16.13 ± 0.95 and 98.97 ± 22.02 µM) to the low- and high-affinity glucose transport systems, respectively. The high-affinity transporters hgt-1/-2 complemented a moderate growth defect under high glucose when glt-1 was deleted. Simultaneous deletion of hgt-1/-2 led to extensive derepression of genes for plant cell wall deconstruction in cells grown on cellulose. The suppression by HGT-1/-2 was connected to both carbon catabolite repression (CCR) and the cyclic adenosine monophosphate-protein kinase A pathway. Alteration of a residue conserved across taxa in hexose transporters resulted in a loss of glucose-transporting function, whereas CCR signal transduction was retained, indicating dual functions for HGT-1/-2 as “transceptors.”ConclusionsIn this study, GLT-1 and HGT-1/-2 were identified as the key components of the glucose dual-affinity transport system, which plays diverse roles in glucose transport and carbon metabolism. Given the wide conservation of the glucose dual-affinity transport system across fungal species, the identification of its components and their pleiotropic roles in this study shed important new light on the molecular basis of nutrient transport, signaling, and plant cell wall degradation in fungi.Electronic supplementary materialThe online version of this article (doi:10.1186/s13068-017-0705-4) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Identification and characterization of the glucose dual-affinity transport system in Neurospora crassa: pleiotropic roles in nutrient transport, signaling, and carbon catabolite repression

Wang

Gao

et al. 2017

Biotechnol Biofuels

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“…In the related mold A. nidulans , that lacks a prtT homolog, the transcription factor XprG regulates extracellular protease production in response to nutrient stress ( Katz et al, 2013 , 2015 ; Katz and Cooper, 2015 ). Deletion of A. nidulans xprG resulted in complete loss of halo formation on skimmed milk (SM) agar plates and an inability to grow on medium containing BSA as sole carbon or nitrogen source.…”

Section: Introductionmentioning

confidence: 99%

“…NDT80 transcription factors are found in animals, fungi, and amoeba. Fungal NDT80 genes were studied in detail in Saccharomyces cerevisiae ( Pak and Segall, 2002 ), Neurospora crassa ( Hutchison and Glass, 2010 ) Candida albicans ( Chen et al, 2004 ; Sellam et al, 2009 , 2010 ) and A. nidulans ( Katz et al, 2013 , 2015 ; Katz and Cooper, 2015 ). The consensus is that in response to nutrient stress and deprivation they activate specific target genes such as proteases, phosphatases, secondary metabolites, and genes involved in meiosis (itself a stress response initiated by starvation) and autolysis.…”

Section: Introductionmentioning

confidence: 99%

Phenotypic and Proteomic Analysis of the Aspergillus fumigatus ΔPrtT, ΔXprG and ΔXprG/ΔPrtT Protease-Deficient Mutants

et al. 2017

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Aspergillus fumigatus is the most common mold species to cause disease in immunocompromised patients. Infection usually begins when its spores (conidia) are inhaled into the airways, where they germinate, forming hyphae that penetrate and destroy the lungs and disseminate to other organs, leading to high mortality. The ability of hyphae to penetrate the pulmonary epithelium is a key step in the infectious process. A. fumigatus produces extracellular proteases that are thought to enhance penetration by degrading host structural barriers. This study explores the role of the A. fumigatus transcription factor XprG in controlling secreted proteolytic activity and fungal virulence. We deleted xprG, alone and in combination with prtT, a transcription factor previously shown to regulate extracellular proteolysis. xprG deletion resulted in abnormal conidiogenesis and formation of lighter colored, more fragile conidia and a moderate reduction in the ability of culture filtrates (CFs) to degrade substrate proteins. Deletion of both xprG and prtT resulted in an additive reduction, generating a mutant strain producing CF with almost no ability to degrade substrate proteins. Detailed proteomic analysis identified numerous secreted proteases regulated by XprG and PrtT, alone and in combination. Interestingly, proteomics also identified reduced levels of secreted cell wall modifying enzymes (glucanases, chitinases) and allergens following deletion of these genes, suggesting they target additional cellular processes. Surprisingly, despite the major alteration in the secretome of the xprG/prtT null mutant, including two to fivefold reductions in the level of 24 proteases, 18 glucanases, 6 chitinases, and 19 allergens, it retained wild-type virulence in murine systemic and pulmonary models of infection. This study highlights the extreme adaptability of A. fumigatus during infection based on extensive gene redundancy.

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“…Carbon starvation–induced autolysis is accompanied by increased expression of the chitinase gene, chiB ( Yamazaki et al 2007 ), therefore this gene can be used as a reporter of autolysis. Unlike the xprGΔ mutant, which has less than 20% of wild-type levels chiB transcript in carbon-starved mycelia, and the xprG1 mutant, which has elevated levels of chiB mRNA in nutrient-sufficient medium ( Katz et al 2015 ), none of the kinase mutants showed altered chiB transcript levels ( Figure 3B ).…”

Section: Resultsmentioning

confidence: 99%

Extreme Diversity in the Regulation of Ndt80-Like Transcription Factors in Fungi

Katz

Cooper

2015

G3 Genes|Genomes|Genetics

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The Saccharomyces cerevisiae Ndt80 protein is the founding member of a class of p53-like transcription factors that is known as the NDT80/PhoG-like DNA-binding family. The number of NDT80-like genes in different fungi is highly variable and their roles, which have been examined in only a few species, include regulation of meiosis, sexual development, biofilm formation, drug resistance, virulence, the response to nutrient stress and programmed cell death. The protein kinase Ime2 regulates the single NDT80 gene present in S. cerevisiae. In this study we used a genetic approach to investigate whether the Aspergillus nidulans Ime2 homolog, ImeB, and/or protein kinases MpkC, PhoA and PhoB regulate the two NDT80-like genes (xprG and ndtA) in A. nidulans. Disruption of imeB, but not mpkC, phoA or phoB, led to increased extracellular protease activity and a defect in mycotoxin production similar to the xprG1 gain-of-function mutation. Quantitative RT-PCR showed that ImeB is a negative regulator of xprG expression and XprG is a negative regulator of xprG and ndtA expression. Thus, in contrast to Ime2, which is a positive regulator of NDT80 in S. cerevisiae, ImeB is a negative regulator as in Neurospora crassa. However, the ability of Ndt80 to autoregulate NDT80 is conserved in A. nidulans though the autoregulatory effect is negative rather than positive. Unlike N. crassa, a null mutation in imeB does not circumvent the requirement for XprG or NdtA. These results show that the regulatory activities of Ime2 and Ndt80-like proteins display an extraordinarily level of evolutionary flexibility.

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Distinct roles for the p53-like transcription factor XprG and autophagy genes in the response to starvation

Cited by 10 publications

References 44 publications

Identification and characterization of the glucose dual-affinity transport system in Neurospora crassa: pleiotropic roles in nutrient transport, signaling, and carbon catabolite repression

Identification and characterization of the glucose dual-affinity transport system in Neurospora crassa: pleiotropic roles in nutrient transport, signaling, and carbon catabolite repression

Phenotypic and Proteomic Analysis of the Aspergillus fumigatus ΔPrtT, ΔXprG and ΔXprG/ΔPrtT Protease-Deficient Mutants

Extreme Diversity in the Regulation of Ndt80-Like Transcription Factors in Fungi

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