Target Of Rapamycin pathway in the white-rot fungus Phanerochaete chrysosporium

Nguyen, Duy Vuong; Roret, Thomas; Fernández-González, Antonio José; Kohler, Annegret; Morel‐Rouhier, Mélanie; Gelhaye, Éric; Sormani, Rodnay

doi:10.1371/journal.pone.0224776

Cited by 14 publications

(8 citation statements)

References 34 publications

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“…Orthologs of Ph. chrysosporium were previously annotated (Nguyen et al 2020). According to a 5'-SAGE study of C. cinerea, TOR pathway members are constantly expressed during the fruiting body formation, except Rheb (C. cinerea protein ID: 493094) a Ras-like small GTPase, which is able to prevent FKBP12 inhibition of TOR (Cheng et al 2013a).…”

Section: Mapk Tor and Camp Pathwaysmentioning

confidence: 99%

Lessons on fruiting body morphogenesis from genomes and transcriptomes of Agaricomycetes

Nagy

Vonk

Künzler

et al. 2021

Preprint

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Fruiting bodies of mushroom-forming fungi (Agaricomycetes) are among the most complex structures produced by fungi. Unlike vegetative hyphae, fruiting bodies grow determinately and follow a genetically encoded developmental program that orchestrates tissue differentiation, growth and sexual sporulation. In spite of more than a century of research, our understanding of the molecular details of fruiting body morphogenesis is limited and a general synthesis on the genetics of this complex process is lacking. In this paper, we aim to comprehensively identify conserved genes related to fruiting body morphogenesis and distill novel functional hypotheses for functionally poorly characterized genes. As a result of this analysis, we report 921 conserved developmentally expressed gene families, only a few dozens of which have previously been reported in fruiting body development. Based on literature data, conserved expression patterns and functional annotations, we provide informed hypotheses on the potential role of these gene families in fruiting body development, yielding the most complete description of molecular processes in fruiting body morphogenesis to date. We discuss genes related to the initiation of fruiting, differentiation, growth, cell surface and cell wall, defense, transcriptional regulation as well as signal transduction. Based on these data we derive a general model of fruiting body development, which includes an early, proliferative phase that is mostly concerned with laying out the mushroom body plan (via cell division and differentiation), and a second phase of growth via cell expansion as well as meiotic events and sporulation. Altogether, our discussions cover 1480 genes of Coprinopsis cinerea, and their orthologs in Agaricus bisporus, Cyclocybe aegerita, Armillaria ostoyae, Auriculariopsis ampla, Laccaria bicolor, Lentinula edodes, Lentinus tigrinus, Mycena kentingensis, Phanerochaete chrysosporium, Pleurotus ostreatus, and Schizophyllum commune, providing functional hypotheses for ~10% of genes in the genomes of these species. Although experimental evidence for the role of these genes will need to be established in the future, our data provide a roadmap for guiding functional analyses of fruiting related genes in the Agaricomycetes. We anticipate that the gene compendium presented here, combined with developments in functional genomics approaches will contribute to uncovering the genetic bases of one of the most spectacular multicellular developmental processes in fungi. Key words: functional annotation; comparative genomics; cell wall remodeling; development; fruiting body morphogenesis; mushroom; transcriptome

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Section: Mapk Tor and Camp Pathwaysmentioning

confidence: 99%

Lessons on fruiting body morphogenesis from genomes and transcriptomes of Agaricomycetes

Nagy

Vonk

Künzler

et al. 2021

Preprint

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“…In addition, another immediate effector of TORC1 is the AGC kinase Sch9, which participates in various cellular functions processes, such as ribosome biosynthesis, translation initiation, and entry into the G 0 phase [22] . The TOR signaling pathway has been documented in various filamentous fungi, including Fusarium graminearum [23–24] , Magnaporthe oryzae [25] , Phanerochaete chrysosporium [26] , Podospora anserine [27] , A. nidulans [28] , A. fumigatus [29–30] , F. fujikuroi [31] , Botrytis cinerea [32] , F. oxysporum [33] , and Mucor circinelloides [34] . However, the TOR signaling pathway has not yet been reported in A. flavus .…”

Section: Introductionmentioning

confidence: 99%

The TOR signaling pathway regulates vegetative development, aflatoxin biosynthesis, and pathogenicity inAspergillus flavus

Cao

Tumukunde

et al. 2023

Preprint

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The target of the rapamycin (TOR) signaling pathway is highly conserved and important in eukaryotes. It is involved in the regulation of various biological processes. However, systematic studies on this pathway in the genus Aspergillus have not been reported. Here, we identified and characterized nine genes encoding components of the TOR pathway in A. flavus, and investigated their biological, genetic and biochemical functions. The FK506-binding protein FKBP3 and its lysine succinylation are important for aflatoxin production and rapamycin resistance. The Tor kinase plays a central role in the global regulation of growth, spore production, aflatoxin biosynthesis and rapamycin stress. As a major downstream effector molecule of Tor kinase, the Sch9 kinase might regulate the calcium and osmotic stress, AFB1 synthesis of A. flavus by its S_TKc, S_TK_X domains and ATP binding site at K340. We also showed that Sch9 kinase might mediate crosstalk between the TOR and the HOG signaling pathways. TapA and TipA, the other downstream components of Tor kinase, play important roles in regulating mycelial growth and sclerotia formation in A. flavus. The member of the TapA-phosphatase complexes Sit4 and Ppg1 are important for hyphal development, sexual reproduction, sclerotia formation, AFB1 biosynthesis, activation of the CWI and TOR signaling pathways in A. flavus. In addition, the another phosphatase complex Nem1/Spo7 play critical role in vegetative growth, conidiation, aflatoxin and LD biogenesis. This study provide new insights into constructing the regulatory network of the TOR signaling pathway and revealing the molecular mechanism of the pathogenicity in A. flavus.

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“…The result is the inhibition of T-cell and B-cell activation leading to immunosuppression. With regards to fungi, the TOR pathway is known to be involved in the response to nutrient resource availability (Cardenas et al, 1999;Bastidas et al, 2012;Nguyen et al, 2020). The serine/threonine kinase TOR is known to interact with two complexes known as TORC1 and TORC2, both of which are known to regulate their targets via phosphorylation (Cardenas et al, 1999;Bastidas et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

“…TORC1 is known to control various cellular processes such as protein synthesis, mRNA synthesis and degradation, autophagy, and nutrient transport; while TORC2 is involved in cell wall integrity and actin polarization (Kubota et al, 2003;Bastidas et al, 2012). TORC1 is the only of the two complexes to be sensitive to rapamycin via a similar pathway involving rapamycin binding to FKBP12 forming a rapamycin-FKBP12 complex that binds to TOR resulting in its inhibition (Bastidas et al, 2012;Nguyen et al, 2020). However, a chronic treatment with rapamycin can not only inhibit TORC1 but also disrupts TORC2 in vivo (Lamming et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

“…However, a chronic treatment with rapamycin can not only inhibit TORC1 but also disrupts TORC2 in vivo (Lamming et al, 2012). In the yeast fungus Saccharomyces cerevisiae, inhibition of TOR via rapamycin exposure results in multiple cellular responses such as protein synthesis inhibition and autophagy triggered by nutrient depletion (Cardenas et al, 1999;Bastidas et al, 2012;Nguyen et al, 2020). Therefore, TOR represents a critical target for the development of new antifungals.…”

Section: Introductionmentioning

confidence: 99%

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Interactions of FK506 and Rapamycin With FK506 Binding Protein 12 in Opportunistic Human Fungal Pathogens

Vellanki

Garcia

Lee

2020

Front. Mol. Biosci.

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Over the past few decades advances in modern medicine have resulted in a global increase in the prevalence of fungal infections. Particularly people undergoing organ transplants or cancer treatments with a compromised immune system are at an elevated risk for lethal fungal infections such as invasive candidiasis, aspergillosis, cryptococcosis, etc. The emergence of drug resistance in fungal pathogens poses a serious threat to mankind and it is critical to identify new targets for the development of antifungals. Calcineurin and TOR proteins are conserved across eukaryotes including pathogenic fungi. Two small molecules FK506 and rapamycin bind to FKBP12 immunophilin and the resulting complexes (FK506-FKBP12 and rapamycin-FKBP12) target calcineurin and TOR, respectively in both humans and fungi. However, due to their immunosuppressive nature these drugs in the current form cannot be used as an antifungal. To overcome this, it is important to identify key differences between human and fungal FKBP12, calcineurin, and TOR proteins which will facilitate the development of new small molecules with higher affinity toward fungal components. The current review highlights FK506/rapamycin-FKBP12 interactions with calcineurin/TOR kinase in human and fungi, and development of non-immunosuppressive analogs of FK506, rapamycin, and novel small molecules in inhibition of fungal calcineurin and TOR kinase.

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Target Of Rapamycin pathway in the white-rot fungus Phanerochaete chrysosporium

Cited by 14 publications

References 34 publications

Lessons on fruiting body morphogenesis from genomes and transcriptomes of Agaricomycetes

Lessons on fruiting body morphogenesis from genomes and transcriptomes of Agaricomycetes

The TOR signaling pathway regulates vegetative development, aflatoxin biosynthesis, and pathogenicity inAspergillus flavus

Interactions of FK506 and Rapamycin With FK506 Binding Protein 12 in Opportunistic Human Fungal Pathogens

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