1887

Abstract

Light is a universal signal perceived by organisms, including fungi, in which light regulates common and unique biological processes depending on the species. Previous research has established that conserved proteins, originally called White collar 1 and 2 from the ascomycete , regulate UV/blue light sensing. Homologous proteins function in distant relatives of , including the basidiomycetes and zygomycetes, which diverged as long as a billion years ago. Here we conducted microarray experiments on the basidiomycete fungus to identify light-regulated genes. Surprisingly, only a single gene was induced by light above the commonly used twofold threshold. This gene, , is predicted to encode a ferrochelatase that catalyses the final step in haem biosynthesis from highly photoreactive porphyrins. The gene complements a Δ strain and is essential for viability, and the Hem15 protein localizes to mitochondria, three lines of evidence that the gene encodes ferrochelatase. Regulation of by light suggests a mechanism by which / mutants are photosensitive and exhibit reduced virulence. We show that ferrochelatase is also light-regulated in a -dependent fashion in and the zygomycete , indicating that ferrochelatase is an ancient target of photoregulation in the fungal kingdom.

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2010-08-01
2019-10-14
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References

  1. Abbas, A. & Labbe-Bois, R. ( 1993; ). Structure-function studies of yeast ferrochelatase. Identification and functional analysis of amino acid substitutions that increase V max and the K M for both substrates. J Biol Chem 268, 8541–8546.
    [Google Scholar]
  2. Almirón, M., Martínez, M., Sanjuan, N. & Ugalde, R. A. ( 2001; ). Ferrochelatase is present in Brucella abortus and is critical for its intracellular survival and virulence. Infect Immun 69, 6225–6230.[CrossRef]
    [Google Scholar]
  3. Bahn, Y.-S., Xue, C., Idnurm, A., Rutherford, J. C., Heitman, J. & Cardenas, M. E. ( 2007; ). Sensing the environment: lessons from fungi. Nat Rev Microbiol 5, 57–69.[CrossRef]
    [Google Scholar]
  4. Bayram, Ö., Krappmann, S., Ni, M., Bok, J. W., Helmstaedt, K., Valerius, O., Braus-Stromeyer, S., Kwon, N. J., Keller, N. P. & other authors ( 2008; ). VelB/VeA/LaeA complex coordinates light signal with fungal development and secondary metabolism. Science 320, 1504–1506.[CrossRef]
    [Google Scholar]
  5. Bergman, K., Eslava, A. P. & Cerdá-Olmedo, E. ( 1973; ). Mutants of Phycomyces with abnormal phototropism. Mol Gen Genet 123, 1–16.[CrossRef]
    [Google Scholar]
  6. Blumenstein, A., Vienken, K., Tasler, R., Purschwitz, J., Veith, D., Frankenberg-Dinkel, N. & Fischer, R. ( 2005; ). The Aspergillus nidulans phytochrome FphA represses sexual development in red light. Curr Biol 15, 1833–1838.[CrossRef]
    [Google Scholar]
  7. Brachmann, C. B., Davies, A., Cost, G. J., Caputo, E., Li, J., Hieter, P. & Boeke, J. D. ( 1998; ). Designer deletion strains derived from Saccharomyces cerevisiae S288C: a useful set of strains and plasmids for PCR-mediated gene disruption and other applications. Yeast 14, 115–132.[CrossRef]
    [Google Scholar]
  8. Camadro, J. M. & Labbé, P. ( 1988; ). Purification and properties of ferrochelatase from the yeast Saccharomyces cerevisiae. Evidence for a precursor form of the protein. J Biol Chem 263, 11675–11682.
    [Google Scholar]
  9. Casadevall, A. & Perfect, J. ( 1998; ). Cryptococcus neoformans. Washington, DC: American Society for Microbiology.
  10. Chen, C.-H., Ringelberg, C. S., Gross, R. H., Dunlap, J. C. & Loros, J. J. ( 2009; ). Genome-wide analysis of light-inducible responses reveals hierarchical light signalling in Neurospora. EMBO J 28, 1029–1042.[CrossRef]
    [Google Scholar]
  11. Christensen, M. K., Falkeid, G., Loros, J. J., Dunlap, J. C., Lillo, C. & Ruoff, P. ( 2004; ). A nitrate-induced frq-less oscillator in Neurospora crassa. J Biol Rhythms 19, 280–286.[CrossRef]
    [Google Scholar]
  12. Corrochano, L. M. ( 2007; ). Fungal photoreceptors: sensory molecules for fungal development and behaviour. Photochem Photobiol Sci 6, 725–736.[CrossRef]
    [Google Scholar]
  13. Cox, T. M. ( 1997; ). Erythropoietic protoporphyria. J Inherit Metab Dis 20, 258–269.[CrossRef]
    [Google Scholar]
  14. de Jesús-Berríos, M., Liu, L., Nussbaum, J. C., Cox, G. M., Stamler, J. S. & Heitman, J. ( 2003; ). Enzymes that counteract nitrosative stress promote fungal virulence. Curr Biol 13, 1963–1968.[CrossRef]
    [Google Scholar]
  15. Degli-Innocenti, F. & Russo, V. E. A. ( 1984; ). Isolation of new white collar mutants of Neurospora crassa and studies on their behavior in the blue light-induced formation of protoperithecia. J Bacteriol 159, 757–761.
    [Google Scholar]
  16. Dong, W., Tang, X., Yu, Y., Nilsen, R., Kim, R., Griffith, J., Arnold, J. & Schüttler, H.-B. ( 2008; ). Systems biology of the clock in Neurospora crassa. PLoS One 3, e3105 [CrossRef]
    [Google Scholar]
  17. Dutta, S., Gerhold, D. L., Rice, M., Germann, M. & Kmiec, E. B. ( 1997; ). The cloning and overexpression of a cruciform binding protein from Ustilago maydis. Biochim Biophys Acta 1352, 258–266.[CrossRef]
    [Google Scholar]
  18. Eldridge, M. G. & Dailey, H. A. ( 1992; ). Yeast ferrochelatase: expression in a baculovirus system and purification of the expression protein. Protein Sci 1, 271–277.
    [Google Scholar]
  19. Fonzi, W. A. & Irwin, M. Y. ( 1993; ). Isogenic strain construction and gene mapping in Candida albicans. Genetics 134, 717–728.
    [Google Scholar]
  20. Froehlich, A. C., Liu, Y., Loros, J. J. & Dunlap, J. C. ( 2002; ). White Collar-1, a circadian blue light photoreceptor, binding to the frequency promoter. Science 297, 815–819.[CrossRef]
    [Google Scholar]
  21. Gora, M., Chaciñska, A., Rytka, J. & Labbe-Bois, R. ( 1996a; ). Isolation and functional characterization of mutant ferrochelatases in Saccharomyces cerevisiae. Biochimie 78, 144–152.[CrossRef]
    [Google Scholar]
  22. Gora, M., Grzybowska, E., Rytka, J. & Labbe-Bois, R. ( 1996b; ). Probing the active-site residues in Saccharomyces cerevisiae ferrochelatase by directed mutagenesis. J Biol Chem 271, 11810–11816.[CrossRef]
    [Google Scholar]
  23. Grenson, M., Mousset, M., Wiame, J. M. & Bechet, J. ( 1966; ). Multiplicity of the amino acid permeases in Saccharomyces cerevisiae. I. Evidence for a specific arginine-transporting system. Biochim Biophys Acta 127, 325–338.[CrossRef]
    [Google Scholar]
  24. Harashima, T. & Heitman, J. ( 2005; ). Gα subunit Gpa2 recruits kelch repeat subunits that inhibit receptor-G protein coupling during cAMP-induced dimorphic transitions in Saccharomyces cerevisiae. Mol Biol Cell 16, 4557–4571.[CrossRef]
    [Google Scholar]
  25. He, Q., Cheng, P., Yang, Y., Wang, L., Gardner, K. H. & Liu, Y. ( 2002; ). White collar-1, a DNA binding transcription factor and a light sensor. Science 297, 840–843.[CrossRef]
    [Google Scholar]
  26. Heintzen, C. & Liu, Y. ( 2007; ). The Neurospora crassa circadian clock. Adv Genet 58, 25–66.
    [Google Scholar]
  27. Heitman, J., Allen, B., Alspaugh, J. A. & Kwon-Chung, K. J. ( 1999; ). On the origins of congenic MATα and MATa strains of the pathogenic yeast Cryptococcus neoformans. Fungal Genet Biol 28, 1–5.[CrossRef]
    [Google Scholar]
  28. Herrera-Estrella, A. & Horwitz, B. A. ( 2007; ). Looking through the eyes of fungi: molecular genetics of photoreception. Mol Microbiol 64, 5–15.[CrossRef]
    [Google Scholar]
  29. Idnurm, A. & Heitman, J. ( 2005; ). Light controls growth and development via a conserved pathway in the fungal kingdom. PLoS Biol 3, e95 [CrossRef]
    [Google Scholar]
  30. Idnurm, A., Reedy, J. L., Nussbaum, J. C. & Heitman, J. ( 2004; ). Cryptococcus neoformans virulence gene discovery through insertional mutagenesis. Eukaryot Cell 3, 420–429.[CrossRef]
    [Google Scholar]
  31. Idnurm, A., Rodríguez-Romero, J., Corrochano, L. M., Sanz, C., Iturriaga, E. A., Eslava, A. P. & Heitman, J. ( 2006; ). The Phycomyces madA gene encodes a blue-light photoreceptor for phototropism and other light responses. Proc Natl Acad Sci U S A 103, 4546–4551.[CrossRef]
    [Google Scholar]
  32. Idnurm, A., Giles, S. S., Perfect, J. R. & Heitman, J. ( 2007; ). Peroxisome function regulates growth on glucose in the basidiomycete fungus Cryptococcus neoformans. Eukaryot Cell 6, 60–72.[CrossRef]
    [Google Scholar]
  33. Jung, W. H., Sham, A., Lian, T., Singh, A., Kosman, D. J. & Kronstad, J. W. ( 2008; ). Iron source preference and regulation of iron uptake in Cryptococcus neoformans. PLoS Pathog 4, e45 [CrossRef]
    [Google Scholar]
  34. Kaasik, K. & Lee, C. C. ( 2004; ). Reciprocal regulation of haem biosynthesis and the circadian clock in mammals. Nature 430, 467–471.[CrossRef]
    [Google Scholar]
  35. Kafer, E. & Fraser, M. ( 1979; ). Isolation and genetic analysis of nuclease halo (nuh) mutants of Neurospora crassa. Mol Gen Genet 169, 117–127.[CrossRef]
    [Google Scholar]
  36. Kauppinen, R. ( 2005; ). Porphyrias. Lancet 365, 241–252.[CrossRef]
    [Google Scholar]
  37. Kirsch, D. R. & Whitney, R. R. ( 1991; ). Pathogenicity of Candida albicans auxotrophic mutants in experimental infections. Infect Immun 59, 3297–3300.
    [Google Scholar]
  38. Ko, Y.-J., Yu, Y. M., Kim, G.-B., Lee, G.-W., Maeng, P. J., Kim, S., Floyd, A., Heitman, J. & Bahn, Y.-S. ( 2009; ). Remodeling of global transcription patterns of Cryptococcus neoformans genes mediated by the stress-activated HOG signaling pathways. Eukaryot Cell 8, 1197–1217.[CrossRef]
    [Google Scholar]
  39. Kwon-Chung, K. J., Edman, J. C. & Wickes, B. L. ( 1992; ). Genetic association of mating types and virulence in Cryptococcus neoformans. Infect Immun 60, 602–605.
    [Google Scholar]
  40. Labbe-Bois, R. ( 1990; ). The ferrochelatase from Saccharomyces cerevisiae. Sequence, disruption, and expression of its structural gene HEM15. J Biol Chem 265, 7278–7283.
    [Google Scholar]
  41. Lewis, Z. A., Correa, A., Schwerdtfeger, C., Link, K. L., Xie, X., Gomer, R. H., Thomas, T., Ebbole, D. J. & Bell-Pedersen, D. ( 2002; ). Overexpression of White Collar-1 (WC-1) activates circadian clock-associated genes, but is not sufficient to induce most light-regulated gene expression in Neurospora crassa. Mol Microbiol 45, 917–931.[CrossRef]
    [Google Scholar]
  42. Li, C. & Schmidhauser, T. J. ( 1995; ). Developmental and photoregulation of al-1 and al-2, structural genes for two enzymes essential for carotenoid biosynthesis in Neurospora. Dev Biol 169, 90–95.[CrossRef]
    [Google Scholar]
  43. Lipson, E. D., Terasaka, D. T. & Silverstein, P. S. ( 1980; ). Double mutants of Phycomyces with abnormal phototropism. Mol Gen Genet 179, 155–162.[CrossRef]
    [Google Scholar]
  44. Loftus, B. J., Fung, E., Roncaglia, P., Rowley, D., Amedeo, P., Bruno, D., Vamathevan, J., Miranda, M., Anderson, I. J. & other authors ( 2005; ). The genome of the basidiomycetous yeast and human pathogen Cryptococcus neoformans. Science 307, 1321–1324.[CrossRef]
    [Google Scholar]
  45. Lu, Y.-K., Sun, K.-H. & Shen, W.-C. ( 2005; ). Blue light negatively regulates the sexual filamentation via the Cwc1 and Cwc2 proteins in Cryptococcus neoformans. Mol Microbiol 56, 480–491.[CrossRef]
    [Google Scholar]
  46. Ma, L.-J., Ibrahim, A. S., Skory, C., Grabherr, M. G., Burger, G., Butler, M., Elias, M., Idnurm, A., Lang, B. F. & other authors ( 2009; ). Genomic analysis of the basal lineage fungus Rhizopus oryzae reveals a whole-genome duplication. PLoS Genet 5, e1000549 [CrossRef]
    [Google Scholar]
  47. McCluskey, K. ( 2003; ). The Fungal Genetics Stock Center: from molds to molecules. Adv Appl Microbiol 52, 245–262.
    [Google Scholar]
  48. McCluskey, K., Wiest, A. & Plamann, M. ( 2010; ). The Fungal Genetics Stock Center: a repository for 50 years of fungal genetics research. J Biosci 35, 119–126.[CrossRef]
    [Google Scholar]
  49. Missall, T. A., Cherry-Harris, J. F. & Lodge, J. K. ( 2005; ). Two glutathione peroxidases in the fungal pathogen Cryptococcus neoformans are expressed in the presence of specific substrates. Microbiology 151, 2573–2581.[CrossRef]
    [Google Scholar]
  50. Miyamoto, K., Nakahigashi, K., Nishimura, K. & Inokuchi, H. ( 1991; ). Isolation and characterization of visible light-sensitive mutants of Escherichia coli K12. J Mol Biol 219, 393–398.[CrossRef]
    [Google Scholar]
  51. Nielsen, K., Cox, G. M., Wang, P., Toffaletti, D. L., Perfect, J. R. & Heitman, J. ( 2003; ). Sexual cycle of Cryptococcus neoformans var. grubii and virulence of congenic a and α isolates. Infect Immun 71, 4831–4841.[CrossRef]
    [Google Scholar]
  52. Nowrousian, M., Duffield, G. E., Loros, J. J. & Dunlap, J. C. ( 2003; ). The frequency gene is required for temperature-dependent regulation of many clock-controlled genes in Neurospora crassa. Genetics 164, 923–933.
    [Google Scholar]
  53. Papenbrock, J., Mock, H.-P., Kruse, E. & Grimm, B. ( 1999; ). Expression studies in tetrapyrrole biosynthesis: inverse maxima of magnesium chelatase and ferrochelatase activity during cyclic photoperiods. Planta 208, 264–273.[CrossRef]
    [Google Scholar]
  54. Purschwitz, J., Müller, S., Kastner, C. & Fischer, R. ( 2006; ). Seeing the rainbow: light sensing in fungi. Curr Opin Microbiol 9, 566–571.[CrossRef]
    [Google Scholar]
  55. Purschwitz, J., Müller, S., Kastner, C., Schöser, M., Haas, H., Espeso, E. A., Atoui, A., Calvo, A. M. & Fischer, R. ( 2008; ). Functional and physical interaction of blue- and red-light sensors in Aspergillus nidulans. Curr Biol 18, 255–259.[CrossRef]
    [Google Scholar]
  56. Purschwitz, J., Müller, S. & Fischer, R. ( 2009; ). Mapping the interaction sites of Aspergillus nidulans phytochrome FphA with the global regulator VeA and the White Collar protein LreB. Mol Genet Genomics 281, 35–42.[CrossRef]
    [Google Scholar]
  57. Ramanan, N. & Wang, Y. ( 2000; ). A high-affinity iron permease essential for Candida albicans virulence. Science 288, 1062–1064.[CrossRef]
    [Google Scholar]
  58. Rodríguez-Romero, J. & Corrochano, L. M. ( 2004; ). The gene for the heat-shock protein HSP100 is induced by blue light and heat-shock in the fungus Phycomyces blakesleeanus. Curr Genet 46, 295–303.[CrossRef]
    [Google Scholar]
  59. Rosales-Saavedra, T., Esquivel-Naranjo, E. U., Casas-Flores, S., Martínez-Hernández, P., Ibarra-Laclette, E., Cortes-Penagos, C. & Herrera-Estrella, A. ( 2006; ). Novel light-regulated genes in Trichoderma atroviride: a dissection by cDNA microarrays. Microbiology 152, 3305–3317.[CrossRef]
    [Google Scholar]
  60. Ruiz-Roldán, M. C., Garre, V., Guarro, J., Mariné, M. & Roncero, M. I. G. ( 2008; ). Role of the white collar 1 photoreceptor in carotenogenesis, UV resistance, hydrophobicity, and virulence of Fusarium oxysporum. Eukaryot Cell 7, 1227–1230.[CrossRef]
    [Google Scholar]
  61. Sano, H., Kaneko, S., Sakamoto, Y., Sato, T. & Shishido, K. ( 2009; ). The basidiomycetous mushroom Lentinula edodes white collar-2 homolog PHRB, a partner of putative blue-light photoreceptor PHRA, binds to a specific site in the promoter region of the L. edodes tyrosinase gene. Fungal Genet Biol 46, 333–341.[CrossRef]
    [Google Scholar]
  62. Sanz, C., Rodríguez-Romero, J., Idnurm, A., Christie, J. M., Heitman, J., Corrochano, L. M. & Eslava, A. P. ( 2009; ). A photoreceptor complex for fungal phototropism: the Phycomyces MADB protein is a WC-2 homolog that interacts with the MADA photoreceptor. Proc Natl Acad Sci U S A 106, 7095–7100.[CrossRef]
    [Google Scholar]
  63. Shen, W.-C., Davidson, R. C., Cox, G. M. & Heitman, J. ( 2002; ). Pheromones stimulate mating and differentiation via paracrine and autocrine signaling in Cryptococcus neoformans. Eukaryot Cell 1, 366–377.[CrossRef]
    [Google Scholar]
  64. Sia, R. A., Lengeler, K. B. & Heitman, J. ( 2000; ). Diploid strains of the pathogenic basidiomycete Cryptococcus neoformans are thermally dimorphic. Fungal Genet Biol 29, 153–163.[CrossRef]
    [Google Scholar]
  65. Silva, F., Torres-Martínez, S. & Garre, V. ( 2006; ). Distinct white collar-1 genes control specific light responses in Mucor circinelloides. Mol Microbiol 61, 1023–1037.[CrossRef]
    [Google Scholar]
  66. Silva, F., Navarro, E., Peñaranda, A., Murcia-Flores, L., Torres-Martínez, S. & Garre, V. ( 2008; ). A RING-finger protein regulates carotenogenesis via proteolysis-independent ubiquitylation of a white collar-1-like activator. Mol Microbiol 70, 1026–1036.
    [Google Scholar]
  67. Solomon, P. S., Jörgens, C. I. & Oliver, R. P. ( 2006; ). δ-Aminolaevulinic acid synthesis is required for virulence of the wheat pathogen Stagonospora nodorum. Microbiology 152, 1533–1538.[CrossRef]
    [Google Scholar]
  68. Swartz, T. E., Tseng, T.-S., Frederickson, M. A., Paris, G., Comerci, D. J., Rajashekara, G., Kim, J. G., Mudgett, M. B., Splitter, G. A. & other authors ( 2007; ). Blue-light-activated histidine kinases: two-component sensors in bacteria. Science 317, 1090–1093.[CrossRef]
    [Google Scholar]
  69. Taylor, J. W. & Berbee, M. L. ( 2006; ). Dating divergences in the fungal tree of life: review and new analyses. Mycologia 98, 838–849.[CrossRef]
    [Google Scholar]
  70. Terashima, K., Yuki, K., Muraguchi, H., Akiyama, M. & Kamada, T. ( 2005; ). The dst1 gene involved in mushroom photomorphogenesis of Coprinus cinereus encodes a putative photoreceptor for blue light. Genetics 171, 101–108.[CrossRef]
    [Google Scholar]
  71. Tisch, D. & Schmoll, M. ( 2010; ). Light regulation of metabolic pathways in fungi. Appl Microbiol Biotechnol 85, 1259–1277.[CrossRef]
    [Google Scholar]
  72. Toffaletti, D. L., Rude, T. H., Johnston, S. A., Durack, D. T. & Perfect, J. R. ( 1993; ). Gene transfer in Cryptococcus neoformans by use of biolistic delivery of DNA. J Bacteriol 175, 1405–1411.
    [Google Scholar]
  73. Wilks, A. & Burkhard, K. A. ( 2007; ). Heme and virulence: how bacterial pathogens regulate, transport and utilize heme. Nat Prod Rep 24, 511–522.[CrossRef]
    [Google Scholar]
  74. Xue, C., Tada, Y., Dong, X. & Heitman, J. ( 2007; ). The human fungal pathogen Cryptococcus can complete its sexual cycle during a pathogenic association with plants. Cell Host Microbe 1, 263–273.[CrossRef]
    [Google Scholar]
  75. Yang, H., Inokuchi, H. & Adler, J. ( 1995; ). Phototaxis away from blue light by an Escherichia coli mutant accumulating protoporphyrin IX. Proc Natl Acad Sci U S A 92, 7332–7336.[CrossRef]
    [Google Scholar]
  76. Yeh, Y.-L., Lin, Y.-S., Su, B.-J. & Shen, W.-C. ( 2009; ). A screening for suppressor mutants reveals components involved in the blue light-inhibited sexual filamentation in Cryptococcus neoformans. Fungal Genet Biol 46, 42–54.[CrossRef]
    [Google Scholar]
  77. Zoladek, T., Nguyen, B. N. & Rytka, J. ( 1996; ). Saccharomyces cerevisiae mutants defective in heme biosynthesis as a tool for studying the mechanism of phototoxicity of porphyrins. Photochem Photobiol 64, 957–962.[CrossRef]
    [Google Scholar]
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