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Light controls growth and development via a conserved pathway in the fungal kingdom.

Idnurm A, Heitman J - PLoS Biol. (2005)

Bottom Line: One UV-sensitive mutant that filaments equally well in the light and the dark was identified and found to have an insertion in the BWC2 gene, whose product is structurally similar to N. crassa WC-2.Deletion of BWC1 or BWC2 reduces the virulence of C. neoformans in a murine model of infection; the Bwc1-Bwc2 system thus represents a novel protein complex that influences both development and virulence in a pathogenic fungus.These results demonstrate that a role for blue/UV light in controlling development is an ancient process that predates the divergence of the fungi into the ascomycete and basidiomycete phyla.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Genetics and Microbiology, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina, USA.

ABSTRACT
Light inhibits mating and haploid fruiting of the human fungal pathogen Cryptococcus neoformans, but the mechanisms involved were unknown. Two genes controlling light responses were discovered through candidate gene and insertional mutagenesis approaches. Deletion of candidate genes encoding a predicted opsin or phytochrome had no effect on mating, while strains mutated in the white collar 1 homolog gene BWC1 mated equally well in the light or the dark. The predicted Bwc1 protein shares identity with Neurospora crassa WC-1, but lacks the zinc finger DNA binding domain. BWC1 regulates cell fusion and repression of hyphal development after fusion in response to blue light. In addition, bwc1 mutant strains are hypersensitive to ultraviolet light. To identify other components required for responses to light, a novel self-fertile haploid strain was created and subjected to Agrobacterium-mediated insertional mutagenesis. One UV-sensitive mutant that filaments equally well in the light and the dark was identified and found to have an insertion in the BWC2 gene, whose product is structurally similar to N. crassa WC-2. The C. neoformans Bwc1 and Bwc2 proteins interact in the yeast two-hybrid assay. Deletion of BWC1 or BWC2 reduces the virulence of C. neoformans in a murine model of infection; the Bwc1-Bwc2 system thus represents a novel protein complex that influences both development and virulence in a pathogenic fungus. These results demonstrate that a role for blue/UV light in controlling development is an ancient process that predates the divergence of the fungi into the ascomycete and basidiomycete phyla.

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A Model of How Two Fungi May Respond to LightThe Bwc1-Bwc2 interaction of C. neoformans shares conserved features with the WC-1-WC-2 interaction of N. crassa but also exhibits unique functional characteristics. In this model, C. neoformans Bwc1-Bwc2 bind to DNA in the dark and act as weak repressors to reduce filament development. We hypothesize that photons perceived through a proposed flavin moiety on Bwc1 cause a conformational change that increases repression of filament formation and cell fusion, and activates transcription of genes required for UV resistance. Alternatively, UV sensitivity may be mediated through repression by Bwc1-Bwc2 of a repressor protein. The N. crassa model is simplified from [3]: a complex of two units of WC-1 forms in response to light to cause an initial up-regulation of frq transcription above the levels occurring in the dark (FRQ feedback inhibits the White collar complex). The complex also increases transcription of genes required for other processes.
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pbio-0030095-g009: A Model of How Two Fungi May Respond to LightThe Bwc1-Bwc2 interaction of C. neoformans shares conserved features with the WC-1-WC-2 interaction of N. crassa but also exhibits unique functional characteristics. In this model, C. neoformans Bwc1-Bwc2 bind to DNA in the dark and act as weak repressors to reduce filament development. We hypothesize that photons perceived through a proposed flavin moiety on Bwc1 cause a conformational change that increases repression of filament formation and cell fusion, and activates transcription of genes required for UV resistance. Alternatively, UV sensitivity may be mediated through repression by Bwc1-Bwc2 of a repressor protein. The N. crassa model is simplified from [3]: a complex of two units of WC-1 forms in response to light to cause an initial up-regulation of frq transcription above the levels occurring in the dark (FRQ feedback inhibits the White collar complex). The complex also increases transcription of genes required for other processes.

Mentions: We propose a model for Bwc1-Bwc2 function that is similar to that of WC-1-WC-2 of N. crassa but differs in several key features (Figure 9). In this model, C. neoformans Bwc1-Bwc2 bind to DNA in the dark and act as weak repressors to reduce filament development. We hypothesize that photons perceived through a flavin cofactor cause a conformational change that enhances repression of filament formation and cell fusion, and activates transcription of genes required for UV resistance/DNA repair. It is also formally possible that light causes Bwc1-Bwc2 to increase transcription of a gene that functions to repress mating, and/or represses transcription of a repressor of UV sensitivity. The N. crassa model is similar but differs in several key features. Recent evidence suggests that a complex of two subunits of WC-1 and one subunit of WC-2 form in response to light [3,10]. The complex positively regulates transcription of genes required for conidiation, mating, and carotenoid production, in marked contrast to the negative regulation of mating observed in C. neoformans. Another difference is that wc-1 is light-regulated in N. crassa, while BWC2 is light-regulated in C. neoformans and BWC1 is not. The N. crassa complex also regulates transcription of frq, and the FRQ protein feedback inhibits the complex, thereby contributing to the wiring of the circadian clock. The roles for WC-1 and WC-2 in N. crassa photoperception also change during the day, adding to the challenge of elucidating their functions. Future studies in C. neoformans will define downstream targets of Bwc1-Bwc2, regulation of Bwc1 and Bwc2 and their complex, and the creation of alleles of Bwc1 bearing mutations in the predicted flavin interacting domain to elucidate the proposed roles of these proteins in light perception.


Light controls growth and development via a conserved pathway in the fungal kingdom.

Idnurm A, Heitman J - PLoS Biol. (2005)

A Model of How Two Fungi May Respond to LightThe Bwc1-Bwc2 interaction of C. neoformans shares conserved features with the WC-1-WC-2 interaction of N. crassa but also exhibits unique functional characteristics. In this model, C. neoformans Bwc1-Bwc2 bind to DNA in the dark and act as weak repressors to reduce filament development. We hypothesize that photons perceived through a proposed flavin moiety on Bwc1 cause a conformational change that increases repression of filament formation and cell fusion, and activates transcription of genes required for UV resistance. Alternatively, UV sensitivity may be mediated through repression by Bwc1-Bwc2 of a repressor protein. The N. crassa model is simplified from [3]: a complex of two units of WC-1 forms in response to light to cause an initial up-regulation of frq transcription above the levels occurring in the dark (FRQ feedback inhibits the White collar complex). The complex also increases transcription of genes required for other processes.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC1064852&req=5

pbio-0030095-g009: A Model of How Two Fungi May Respond to LightThe Bwc1-Bwc2 interaction of C. neoformans shares conserved features with the WC-1-WC-2 interaction of N. crassa but also exhibits unique functional characteristics. In this model, C. neoformans Bwc1-Bwc2 bind to DNA in the dark and act as weak repressors to reduce filament development. We hypothesize that photons perceived through a proposed flavin moiety on Bwc1 cause a conformational change that increases repression of filament formation and cell fusion, and activates transcription of genes required for UV resistance. Alternatively, UV sensitivity may be mediated through repression by Bwc1-Bwc2 of a repressor protein. The N. crassa model is simplified from [3]: a complex of two units of WC-1 forms in response to light to cause an initial up-regulation of frq transcription above the levels occurring in the dark (FRQ feedback inhibits the White collar complex). The complex also increases transcription of genes required for other processes.
Mentions: We propose a model for Bwc1-Bwc2 function that is similar to that of WC-1-WC-2 of N. crassa but differs in several key features (Figure 9). In this model, C. neoformans Bwc1-Bwc2 bind to DNA in the dark and act as weak repressors to reduce filament development. We hypothesize that photons perceived through a flavin cofactor cause a conformational change that enhances repression of filament formation and cell fusion, and activates transcription of genes required for UV resistance/DNA repair. It is also formally possible that light causes Bwc1-Bwc2 to increase transcription of a gene that functions to repress mating, and/or represses transcription of a repressor of UV sensitivity. The N. crassa model is similar but differs in several key features. Recent evidence suggests that a complex of two subunits of WC-1 and one subunit of WC-2 form in response to light [3,10]. The complex positively regulates transcription of genes required for conidiation, mating, and carotenoid production, in marked contrast to the negative regulation of mating observed in C. neoformans. Another difference is that wc-1 is light-regulated in N. crassa, while BWC2 is light-regulated in C. neoformans and BWC1 is not. The N. crassa complex also regulates transcription of frq, and the FRQ protein feedback inhibits the complex, thereby contributing to the wiring of the circadian clock. The roles for WC-1 and WC-2 in N. crassa photoperception also change during the day, adding to the challenge of elucidating their functions. Future studies in C. neoformans will define downstream targets of Bwc1-Bwc2, regulation of Bwc1 and Bwc2 and their complex, and the creation of alleles of Bwc1 bearing mutations in the predicted flavin interacting domain to elucidate the proposed roles of these proteins in light perception.

Bottom Line: One UV-sensitive mutant that filaments equally well in the light and the dark was identified and found to have an insertion in the BWC2 gene, whose product is structurally similar to N. crassa WC-2.Deletion of BWC1 or BWC2 reduces the virulence of C. neoformans in a murine model of infection; the Bwc1-Bwc2 system thus represents a novel protein complex that influences both development and virulence in a pathogenic fungus.These results demonstrate that a role for blue/UV light in controlling development is an ancient process that predates the divergence of the fungi into the ascomycete and basidiomycete phyla.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Genetics and Microbiology, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina, USA.

ABSTRACT
Light inhibits mating and haploid fruiting of the human fungal pathogen Cryptococcus neoformans, but the mechanisms involved were unknown. Two genes controlling light responses were discovered through candidate gene and insertional mutagenesis approaches. Deletion of candidate genes encoding a predicted opsin or phytochrome had no effect on mating, while strains mutated in the white collar 1 homolog gene BWC1 mated equally well in the light or the dark. The predicted Bwc1 protein shares identity with Neurospora crassa WC-1, but lacks the zinc finger DNA binding domain. BWC1 regulates cell fusion and repression of hyphal development after fusion in response to blue light. In addition, bwc1 mutant strains are hypersensitive to ultraviolet light. To identify other components required for responses to light, a novel self-fertile haploid strain was created and subjected to Agrobacterium-mediated insertional mutagenesis. One UV-sensitive mutant that filaments equally well in the light and the dark was identified and found to have an insertion in the BWC2 gene, whose product is structurally similar to N. crassa WC-2. The C. neoformans Bwc1 and Bwc2 proteins interact in the yeast two-hybrid assay. Deletion of BWC1 or BWC2 reduces the virulence of C. neoformans in a murine model of infection; the Bwc1-Bwc2 system thus represents a novel protein complex that influences both development and virulence in a pathogenic fungus. These results demonstrate that a role for blue/UV light in controlling development is an ancient process that predates the divergence of the fungi into the ascomycete and basidiomycete phyla.

Show MeSH
Related in: MedlinePlus