The monothiol glutaredoxin GrxD is essential for sensing iron starvation in Aspergillus fumigatus.

Abstract:

:Efficient adaptation to iron starvation is an essential virulence determinant of the most common human mold pathogen, Aspergillus fumigatus. Here, we demonstrate that the cytosolic monothiol glutaredoxin GrxD plays an essential role in iron sensing in this fungus. Our studies revealed that (i) GrxD is essential for growth; (ii) expression of the encoding gene, grxD, is repressed by the transcription factor SreA in iron replete conditions and upregulated during iron starvation; (iii) during iron starvation but not iron sufficiency, GrxD displays predominant nuclear localization; (iv) downregulation of grxD expression results in de-repression of genes involved in iron-dependent pathways and repression of genes involved in iron acquisition during iron starvation, but did not significantly affect these genes during iron sufficiency; (v) GrxD displays protein-protein interaction with components of the cytosolic iron-sulfur cluster biosynthetic machinery, indicating a role in this process, and with the transcription factors SreA and HapX, which mediate iron regulation of iron acquisition and iron-dependent pathways; (vi) UV-Vis spectra of recombinant HapX or the complex of HapX and GrxD indicate coordination of iron-sulfur clusters; (vii) the cysteine required for iron-sulfur cluster coordination in GrxD is in vitro dispensable for interaction with HapX; and (viii) there is a GrxD-independent mechanism for sensing iron sufficiency by HapX; (ix) inactivation of SreA suppresses the lethal effect caused by GrxD inactivation. Taken together, this study demonstrates that GrxD is crucial for iron homeostasis in A. fumigatus.

journal_name

PLoS Genet

journal_title

PLoS genetics

authors

Misslinger M,Scheven MT,Hortschansky P,López-Berges MS,Heiss K,Beckmann N,Heigl T,Hermann M,Krüger T,Kniemeyer O,Brakhage AA,Haas H

doi

10.1371/journal.pgen.1008379

subject

Has Abstract

pub_date

2019-09-16 00:00:00

pages

e1008379

issue

9

eissn

1553-7390

issn

1553-7404

pii

PGENETICS-D-19-00362

journal_volume

15

pub_type

杂志文章
  • Alternative epigenetic chromatin states of polycomb target genes.

    abstract::Polycomb (PcG) regulation has been thought to produce stable long-term gene silencing. Genomic analyses in Drosophila and mammals, however, have shown that it targets many genes, which can switch state during development. Genetic evidence indicates that critical for the active state of PcG target genes are the histone...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1000805

    authors: Schwartz YB,Kahn TG,Stenberg P,Ohno K,Bourgon R,Pirrotta V

    更新日期:2010-01-01 00:00:00

  • The secreted immunoglobulin domain proteins ZIG-5 and ZIG-8 cooperate with L1CAM/SAX-7 to maintain nervous system integrity.

    abstract::During nervous system development, neuronal cell bodies and their axodendritic projections are precisely positioned through transiently expressed patterning cues. We show here that two neuronally expressed, secreted immunoglobulin (Ig) domain-containing proteins, ZIG-5 and ZIG-8, have no detectable role during embryon...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1002819

    authors: Bénard CY,Blanchette C,Recio J,Hobert O

    更新日期:2012-01-01 00:00:00

  • Dual function of perivascular fibroblasts in vascular stabilization in zebrafish.

    abstract::Blood vessels are vital to sustain life in all vertebrates. While it is known that mural cells (pericytes and smooth muscle cells) regulate vascular integrity, the contribution of other cell types to vascular stabilization has been largely unexplored. Using zebrafish, we identified sclerotome-derived perivascular fibr...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1008800

    authors: Rajan AM,Ma RC,Kocha KM,Zhang DJ,Huang P

    更新日期:2020-10-26 00:00:00

  • Inflammation-mediated genetic and epigenetic alterations drive cancer development in the neighboring epithelium upon stromal abrogation of TGF-β signaling.

    abstract::Deletion of tumor suppressor genes in stromal fibroblasts induces epithelial cancer development, suggesting an important role of stroma in epithelial homoeostasis. However, the underlying mechanisms remain to be elucidated. Here we report that deletion of the gene encoding TGFβ receptor 2 (Tgfbr2) in the stromal fibro...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1003251

    authors: Achyut BR,Bader DA,Robles AI,Wangsa D,Harris CC,Ried T,Yang L

    更新日期:2013-01-01 00:00:00

  • Glucocorticoid receptor-dependent gene regulatory networks.

    abstract::While the molecular mechanisms of glucocorticoid regulation of transcription have been studied in detail, the global networks regulated by the glucocorticoid receptor (GR) remain unknown. To address this question, we performed an orthogonal analysis to identify direct targets of the GR. First, we analyzed the expressi...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.0010016

    authors: Phuc Le P,Friedman JR,Schug J,Brestelli JE,Parker JB,Bochkis IM,Kaestner KH

    更新日期:2005-08-01 00:00:00

  • Mutations in MAB21L2 result in ocular Coloboma, microcornea and cataracts.

    abstract::Ocular coloboma results from abnormal embryonic development and is often associated with additional ocular and systemic features. Coloboma is a highly heterogeneous disorder with many cases remaining unexplained. Whole exome sequencing from two cousins affected with dominant coloboma with microcornea, cataracts, and s...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1005002

    authors: Deml B,Kariminejad A,Borujerdi RH,Muheisen S,Reis LM,Semina EV

    更新日期:2015-02-26 00:00:00

  • Coordination of chromatid separation and spindle elongation by antagonistic activities of mitotic and S-phase CDKs.

    abstract::Because cohesion prevents sister-chromatid separation and spindle elongation, cohesion dissolution may trigger these two events simultaneously. However, the relatively normal spindle elongation kinetics in yeast cohesin mutants indicates an additional mechanism for the temporal control of spindle elongation. Here we s...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1003319

    authors: Liang F,Richmond D,Wang Y

    更新日期:2013-01-01 00:00:00

  • A positive feedback loop links opposing functions of P-TEFb/Cdk9 and histone H2B ubiquitylation to regulate transcript elongation in fission yeast.

    abstract::Transcript elongation by RNA polymerase II (RNAPII) is accompanied by conserved patterns of histone modification. Whereas histone modifications have established roles in transcription initiation, their functions during elongation are not understood. Mono-ubiquitylation of histone H2B (H2Bub1) plays a key role in coord...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1002822

    authors: Sansó M,Lee KM,Viladevall L,Jacques PÉ,Pagé V,Nagy S,Racine A,St Amour CV,Zhang C,Shokat KM,Schwer B,Robert F,Fisher RP,Tanny JC

    更新日期:2012-01-01 00:00:00

  • Binary addition in a living cell based on riboregulation.

    abstract::Synthetic biology aims at (re-)programming living cells like computers to perform new functions for a variety of applications. Initial work rested on transcription factors, but regulatory RNAs have recently gained much attention due to their high programmability. However, functional circuits mainly implemented with re...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1007548

    authors: Rosado A,Cordero T,Rodrigo G

    更新日期:2018-07-19 00:00:00

  • The POU factor ventral veins lacking/Drifter directs the timing of metamorphosis through ecdysteroid and juvenile hormone signaling.

    abstract::Although endocrine changes are known to modulate the timing of major developmental transitions, the genetic mechanisms underlying these changes remain poorly understood. In insects, two developmental hormones, juvenile hormone (JH) and ecdysteroids, are coordinated with each other to induce developmental changes assoc...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004425

    authors: Cheng C,Ko A,Chaieb L,Koyama T,Sarwar P,Mirth CK,Smith WA,Suzuki Y

    更新日期:2014-06-19 00:00:00

  • Parallel evolution of a type IV secretion system in radiating lineages of the host-restricted bacterial pathogen Bartonella.

    abstract::Adaptive radiation is the rapid origination of multiple species from a single ancestor as the result of concurrent adaptation to disparate environments. This fundamental evolutionary process is considered to be responsible for the genesis of a great portion of the diversity of life. Bacteria have evolved enormous biol...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1001296

    authors: Engel P,Salzburger W,Liesch M,Chang CC,Maruyama S,Lanz C,Calteau A,Lajus A,Médigue C,Schuster SC,Dehio C

    更新日期:2011-02-10 00:00:00

  • Loss of the RNA trimethylguanosine cap is compatible with nuclear accumulation of spliceosomal snRNAs but not pre-mRNA splicing or snRNA processing during animal development.

    abstract::The 2,2,7-trimethylguanosine (TMG) cap is one of the first identified modifications on eukaryotic RNAs. TMG, synthesized by the conserved Tgs1 enzyme, is abundantly present on snRNAs essential for pre-mRNA splicing. Results from ex vivo experiments in vertebrate cells suggested that TMG ensures nuclear localization of...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1009098

    authors: Cheng L,Zhang Y,Zhang Y,Chen T,Xu YZ,Rong YS

    更新日期:2020-10-21 00:00:00

  • An allele of an ancestral transcription factor dependent on a horizontally acquired gene product.

    abstract::Changes in gene regulatory circuits often give rise to phenotypic differences among closely related organisms. In bacteria, these changes can result from alterations in the ancestral genome and/or be brought about by genes acquired by horizontal transfer. Here, we identify an allele of the ancestral transcription fact...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1003060

    authors: Chen HD,Jewett MW,Groisman EA

    更新日期:2012-01-01 00:00:00

  • The CUGBP2 splicing factor regulates an ensemble of branchpoints from perimeter binding sites with implications for autoregulation.

    abstract::Alternative pre-mRNA splicing adjusts the transcriptional output of the genome by generating related mRNAs from a single primary transcript, thereby expanding protein diversity. A fundamental unanswered question is how splicing factors achieve specificity in the selection of target substrates despite the recognition o...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1000595

    authors: Dembowski JA,Grabowski PJ

    更新日期:2009-08-01 00:00:00

  • Papillorenal syndrome-causing missense mutations in PAX2/Pax2 result in hypomorphic alleles in mouse and human.

    abstract::Papillorenal syndrome (PRS, also known as renal-coloboma syndrome) is an autosomal dominant disease characterized by potentially-blinding congenital optic nerve excavation and congenital kidney abnormalities. Many patients with PRS have mutations in the paired box transcription factor gene, PAX2. Although most mutatio...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1000870

    authors: Alur RP,Vijayasarathy C,Brown JD,Mehtani M,Onojafe IF,Sergeev YV,Boobalan E,Jones M,Tang K,Liu H,Xia CH,Gong X,Brooks BP

    更新日期:2010-03-05 00:00:00

  • Ku Binding on Telomeres Occurs at Sites Distal from the Physical Chromosome Ends.

    abstract::The Ku complex binds non-specifically to DNA breaks and ensures repair via NHEJ. However, Ku is also known to bind directly to telomeric DNA ends and its presence there is associated with telomere capping, but avoiding NHEJ. How the complex discriminates between a DNA break and a telomeric extremity remains unknown. O...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1006479

    authors: Larcher MV,Pasquier E,MacDonald RS,Wellinger RJ

    更新日期:2016-12-08 00:00:00

  • CRP-cAMP mediates silencing of Salmonella virulence at the post-transcriptional level.

    abstract::Invasion of epithelial cells by Salmonella enterica requires expression of genes located in the pathogenicity island I (SPI-1). The expression of SPI-1 genes is very tightly regulated and activated only under specific conditions. Most studies have focused on the regulatory pathways that induce SPI-1 expression. Here, ...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1007401

    authors: El Mouali Y,Gaviria-Cantin T,Sánchez-Romero MA,Gibert M,Westermann AJ,Vogel J,Balsalobre C

    更新日期:2018-06-07 00:00:00

  • MMS exposure promotes increased MtDNA mutagenesis in the presence of replication-defective disease-associated DNA polymerase γ variants.

    abstract::Mitochondrial DNA (mtDNA) encodes proteins essential for ATP production. Mutant variants of the mtDNA polymerase cause mutagenesis that contributes to aging, genetic diseases, and sensitivity to environmental agents. We interrogated mtDNA replication in Saccharomyces cerevisiae strains with disease-associated mutation...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004748

    authors: Stumpf JD,Copeland WC

    更新日期:2014-10-23 00:00:00

  • Checkpoint Activation of an Unconventional DNA Replication Program in Tetrahymena.

    abstract::The intra-S phase checkpoint kinase of metazoa and yeast, ATR/MEC1, protects chromosomes from DNA damage and replication stress by phosphorylating subunits of the replicative helicase, MCM2-7. Here we describe an unprecedented ATR-dependent pathway in Tetrahymena thermophila in which the essential pre-replicative comp...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1005405

    authors: Sandoval PY,Lee PH,Meng X,Kapler GM

    更新日期:2015-07-28 00:00:00

  • Abnormal type I collagen post-translational modification and crosslinking in a cyclophilin B KO mouse model of recessive osteogenesis imperfecta.

    abstract::Cyclophilin B (CyPB), encoded by PPIB, is an ER-resident peptidyl-prolyl cis-trans isomerase (PPIase) that functions independently and as a component of the collagen prolyl 3-hydroxylation complex. CyPB is proposed to be the major PPIase catalyzing the rate-limiting step in collagen folding. Mutations in PPIB cause re...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004465

    authors: Cabral WA,Perdivara I,Weis M,Terajima M,Blissett AR,Chang W,Perosky JE,Makareeva EN,Mertz EL,Leikin S,Tomer KB,Kozloff KM,Eyre DR,Yamauchi M,Marini JC

    更新日期:2014-06-26 00:00:00

  • A Minimal Threshold of c-di-GMP Is Essential for Fruiting Body Formation and Sporulation in Myxococcus xanthus.

    abstract::Generally, the second messenger bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) regulates the switch between motile and sessile lifestyles in bacteria. Here, we show that c-di-GMP is an essential regulator of multicellular development in the social bacterium Myxococcus xanthus. In response to starvation, M. xanthus initiate...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1006080

    authors: Skotnicka D,Smaldone GT,Petters T,Trampari E,Liang J,Kaever V,Malone JG,Singer M,Søgaard-Andersen L

    更新日期:2016-05-23 00:00:00

  • A Novel Feedback Loop That Controls Bimodal Expression of Genetic Competence.

    abstract::Gene expression can be highly heterogeneous in isogenic cell populations. An extreme type of heterogeneity is the so-called bistable or bimodal expression, whereby a cell can differentiate into two alternative expression states. Stochastic fluctuations of protein levels, also referred to as noise, provide the necessar...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1005047

    authors: Gamba P,Jonker MJ,Hamoen LW

    更新日期:2015-06-25 00:00:00

  • Effects of aneuploidy on genome structure, expression, and interphase organization in Arabidopsis thaliana.

    abstract::Aneuploidy refers to losses and/or gains of individual chromosomes from the normal chromosome set. The resulting gene dosage imbalance has a noticeable affect on the phenotype, as illustrated by aneuploid syndromes, including Down syndrome in humans, and by human solid tumor cells, which are highly aneuploid. Although...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1000226

    authors: Huettel B,Kreil DP,Matzke M,Matzke AJ

    更新日期:2008-10-01 00:00:00

  • Gene Expression Differences in Prostate Cancers between Young and Old Men.

    abstract::Prostate cancer incidence is increasing in younger men. We investigated whether men diagnosed with Gleason 7 (3+4) T2 prostate cancer at younger ages (≤ 45 years, young cohort) had different mRNA and miRNA expression profiles than men diagnosed at older ages (71-74 years, older cohort). We identified differentially ex...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1006477

    authors: Ding Y,Wu H,Warden C,Steele L,Liu X,Iterson MV,Wu X,Nelson R,Liu Z,Yuan YC,Neuhausen SL

    更新日期:2016-12-27 00:00:00

  • Coordinate regulation of stem cell competition by Slit-Robo and JAK-STAT signaling in the Drosophila testis.

    abstract::Stem cells in tissues reside in and receive signals from local microenvironments called niches. Understanding how multiple signals within niches integrate to control stem cell function is challenging. The Drosophila testis stem cell niche consists of somatic hub cells that maintain both germline stem cells and somatic...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004713

    authors: Stine RR,Greenspan LJ,Ramachandran KV,Matunis EL

    更新日期:2014-11-06 00:00:00

  • Aconitase causes iron toxicity in Drosophila pink1 mutants.

    abstract::The PTEN-induced kinase 1 (PINK1) is a mitochondrial kinase, and pink1 mutations cause early onset Parkinson's disease (PD) in humans. Loss of pink1 in Drosophila leads to defects in mitochondrial function, and genetic data suggest that another PD-related gene product, Parkin, acts with pink1 to regulate the clearance...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1003478

    authors: Esposito G,Vos M,Vilain S,Swerts J,De Sousa Valadas J,Van Meensel S,Schaap O,Verstreken P

    更新日期:2013-04-01 00:00:00

  • Reversible Oxidation of a Conserved Methionine in the Nuclear Export Sequence Determines Subcellular Distribution and Activity of the Fungal Nitrate Regulator NirA.

    abstract::The assimilation of nitrate, a most important soil nitrogen source, is tightly regulated in microorganisms and plants. In Aspergillus nidulans, during the transcriptional activation process of nitrate assimilatory genes, the interaction between the pathway-specific transcription factor NirA and the exportin KapK/CRM1 ...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1005297

    authors: Gallmetzer A,Silvestrini L,Schinko T,Gesslbauer B,Hortschansky P,Dattenböck C,Muro-Pastor MI,Kungl A,Brakhage AA,Scazzocchio C,Strauss J

    更新日期:2015-07-01 00:00:00

  • The genetic architecture of the genome-wide transcriptional response to ER stress in the mouse.

    abstract::Endoplasmic reticulum (ER) stress occurs when misfolded proteins accumulate in the ER. The cellular response to ER stress involves complex transcriptional and translational changes, important to the survival of the cell. ER stress is a primary cause and a modifier of many human diseases. A first step to understanding ...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004924

    authors: Chow CY,Wang X,Riccardi D,Wolfner MF,Clark AG

    更新日期:2015-02-04 00:00:00

  • Interactions with iridophores and the tissue environment required for patterning melanophores and xanthophores during zebrafish adult pigment stripe formation.

    abstract::Skin pigment patterns of vertebrates are a classic system for understanding fundamental mechanisms of morphogenesis, differentiation, and pattern formation, and recent studies of zebrafish have started to elucidate the cellular interactions and molecular mechanisms underlying these processes. In this species, horizont...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1003561

    authors: Patterson LB,Parichy DM

    更新日期:2013-05-01 00:00:00

  • Glial loss of the metallo β-lactamase domain containing protein, SWIP-10, induces age- and glutamate-signaling dependent, dopamine neuron degeneration.

    abstract::Across phylogeny, glutamate (Glu) signaling plays a critical role in regulating neural excitability, thus supporting many complex behaviors. Perturbed synaptic and extrasynaptic Glu homeostasis in the human brain has been implicated in multiple neuropsychiatric and neurodegenerative disorders including Parkinson's dis...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1007269

    authors: Gibson CL,Balbona JT,Niedzwiecki A,Rodriguez P,Nguyen KCQ,Hall DH,Blakely RD

    更新日期:2018-03-28 00:00:00