1887

Abstract

Heterokaryon incompatibility (HI) is a nonself recognition phenomenon occurring in filamentous fungi that is important for limiting resource plundering and restricting viral transfer between strains. Nonself recognition and HI occurs during hyphal fusion between strains that differ at loci. If two strains undergo hyphal fusion, but differ in allelic specificity at a locus, the fusion cell is compartmentalized and undergoes a rapid programmed cell death (PCD). Incompatible heterokaryons show a macroscopic phenotype of slow growth and diminished conidiation, and a microscopic phenotype of hyphal compartmentation and cell death. To understand processes associated with HI and PCD, we used whole-genome microarrays for to assess transcriptional differences associated with induction of HI mediated by differences in haplotype. Our data show that HI is a dynamic and transcriptionally active process. The production of reactive oxygen species is implicated in the execution of HI and PCD in , as are several genes involved in phosphatidylinositol and calcium signalling pathways. However, genes encoding mammalian homologues of caspases or apoptosis-inducing factor (AIF) are not required for HI or programmed cell death. These data indicate that PCD during HI occurs via a novel and possibly fungal-specific mechanism, making this pathway an attractive drug target for control of fungal infections.

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2009-12-01
2024-04-27
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References

  1. Adams J. M. 2003; Ways of dying: multiple pathways to apoptosis. Genes Dev 17:2481–2495
    [Google Scholar]
  2. Arpaia G., Cerri F., Baima S., Macino G. 1999; Involvement of protein kinase C in the response of Neurospora crassa to blue light. Mol Gen Genet 262:314–322
    [Google Scholar]
  3. Biella S., Smith M. L., Aist J. R., Cortesi P., Milgroom M. G. 2002; Programmed cell death correlates with virus transmission in a filamentous fungus. Proc Biol Sci 269:2269–2276
    [Google Scholar]
  4. Borkovich K. A., Alex L. A., Yarden O., Freitag M., Turner G. E., Read N. D., Seiler S., Bell-Pedersen D., Paietta J. other authors 2004; Lessons from the genome sequence of Neurospora crassa: tracing the path from genomic blueprint to multicellular organism. Microbiol Mol Biol Rev 68:1–108
    [Google Scholar]
  5. Castro A., Lemos C., Falcao A., Glass N. L., Videira A. 2008; Increased resistance of complex I mutants to phytosphingosine-induced programmed cell death. J Biol Chem 283:19314–19321
    [Google Scholar]
  6. Chandra J., Samali A., Orrenius S. 2000; Triggering and modulation of apoptosis by oxidative stress. Free Radic Biol Med 29:323–333
    [Google Scholar]
  7. Chen C., Dickman M. B. 2005; Proline suppresses apoptosis in the fungal pathogen Colletotrichum trifolii . Proc Natl Acad Sci U S A 102:3459–3464
    [Google Scholar]
  8. Cheng J., Park T. S., Chio L. C., Fischl A. S., Ye X. S. 2003; Induction of apoptosis by sphingoid long-chain bases in Aspergillus nidulans . Mol Cell Biol 23:163–177
    [Google Scholar]
  9. Choudhary S., Lee H. C., Maiti M., He Q., Cheng P., Liu Q., Liu Y. 2007; A double-stranded-RNA response program important for RNA interference efficiency. Mol Cell Biol 27:3995–4005
    [Google Scholar]
  10. Cornelius G., Gebauer G., Techel D. 1989; Inositol trisphosphate induces calcium release from Neurospora crassa vacuoles. Biochem Biophys Res Commun 162:852–856
    [Google Scholar]
  11. Debets A. J. M., Griffiths A. J. F. 1998; Polymorphism of het-genes prevents resource plundering in Neurospora crassa . Mycol Res 102:1343–1349
    [Google Scholar]
  12. Debets F., Yang X., Griffiths A. J. F. 1994; Vegetative incompatibility in Neurospora – its effect on horizontal transfer of mitochondrial plasmids and senescence in natural populations. Curr Genet 26:113–119
    [Google Scholar]
  13. Dunlap J. C., Borkovich K. A., Henn M. R., Turner G. E., Sachs M. S., Glass N. L., McCluskey K., Plamann M., Galagan J. E. other authors 2007; Enabling a community to dissect an organism: overview of the Neurospora functional genomics project. Adv Genet 57:49–96
    [Google Scholar]
  14. Eisen M. B., Spellman P. T., Brown P. O., Botstein D. 1998; Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci U S A 95:14863–14868
    [Google Scholar]
  15. Eisenberg T., Büttner S., Kroemer G., Madeo F. 2007; The mitochondrial pathway in yeast apoptosis. Apoptosis 12:1011–1023
    [Google Scholar]
  16. Fedorova N. D., Badger J. H., Robson G. D., Wortman J. R., Nierman W. C. 2005; Comparative analysis of programmed cell death pathways in filamentous fungi. BMC Genomics 6:177
    [Google Scholar]
  17. Fleissner A., Simonin A. R., Glass N. L. 2008; Cell fusion in the filamentous fungus, Neurospora crassa . Methods Mol Biol 475:21–38
    [Google Scholar]
  18. Garnjobst L., Wilson J. F. 1956; Heterocaryosis and protoplasmic incompatibility in Neurospora crassa . Proc Natl Acad Sci U S A 42:613–618
    [Google Scholar]
  19. Glass N. L., Dementhon K. 2006; Non-self recognition and programmed cell death in filamentous fungi. Curr Opin Microbiol 9:553–558
    [Google Scholar]
  20. Glass N. L., Kaneko I. 2003; Fatal attraction: nonself recognition and heterokaryon incompatibility in filamentous fungi. Eukaryot Cell 2:1–8
    [Google Scholar]
  21. Glass N. L., Rasmussen C., Roca M. G., Read N. D. 2004; Hyphal homing, fusion and mycelial interconnectedness. Trends Microbiol 12:135–141
    [Google Scholar]
  22. Guaragnella N., Pereira C., Sousa M. J., Antonacci L., Passarella S., Corte-Real M., Marra E., Giannattasio S. 2006; YCA1 participates in the acetic acid induced yeast programmed cell death also in a manner unrelated to its caspase-like activity. FEBS Lett 580:6880–6884
    [Google Scholar]
  23. Herker E., Jungwirth H., Lehmann K. A., Maldener C., Fröhlich K. U., Wissing S., Büttner S., Fehr M., Sigrist S., Madeo F. 2004; Chronological aging leads to apoptosis in yeast. J Cell Biol 164:501–507
    [Google Scholar]
  24. Jacobson D. J., Beurkens K., Klomparens K. L. 1998; Microscopic and ultrastructural examination of vegetative incompatibility in partial diploids heterozygous at het loci in Neurospora crassa . Fungal Genet Biol 23:45–56
    [Google Scholar]
  25. Jedd G., Chua N. H. 2000; A new self-assembled peroxisomal vesicle required for efficient resealing of the plasma membrane. Nat Cell Biol 2:226–231
    [Google Scholar]
  26. Jin C., Reed J. C. 2002; Yeast and apoptosis. Nat Rev Mol Cell Biol 3:453–459
    [Google Scholar]
  27. Kaneko I., Dementhon K., Xiang Q., Glass N. L. 2006; Nonallelic interactions between het-c and a polymorphic locus, pin-c, are essential for nonself recognition and programmed cell death in Neurospora crassa . Genetics 172:1545–1555
    [Google Scholar]
  28. Kasuga T., Townsend J. P., Tian C., Gilbert L. B., Mannhaupt G., Taylor J. W., Glass N. L. 2005; Long-oligomer microarray profiling in Neurospora crassa reveals the transcriptional program underlying biochemical and physiological events of conidial germination. Nucleic Acids Res 33:6469–6485
    [Google Scholar]
  29. Khan M. A. S., Chock P. B., Stadtman E. R. 2005; Knockout of caspase-like gene, YCA1, abrogates apoptosis and elevates oxidized proteins in Saccharomyces cerevisiae . Proc Natl Acad Sci U S A 102:17326–17331
    [Google Scholar]
  30. Kimata Y., Yanagida M. 2004; Suppression of a mitotic mutant by tRNA-Ala anticodon mutations that produce a dominant defect in late mitosis. J Cell Sci 117:2283–2293
    [Google Scholar]
  31. LeBel C. P., Ischiropoulos H., Bondy S. C. 1992; Evaluation of the probe 2′,7′-dichlorofluorescin as an indicator of reactive oxygen species formation and oxidative stress. Chem Res Toxicol 5:227–231
    [Google Scholar]
  32. Leiter E., Szappanos H., Oberparleiter C., Kaiserer L., Csernoch L., Pusztahelyi T., Emri T., Pócsi I., Salvenmoser W., Marx F. 2005; Antifungal protein PAF severely affects the integrity of the plasma membrane of Aspergillus nidulans and induces an apoptosis-like phenotype. Antimicrob Agents Chemother 49:2445–2453
    [Google Scholar]
  33. Leslie J. F., Zeller K. A. 1996; Heterokaryon incompatibility in fungi – more than just another way to die. J Genet 75:415–424
    [Google Scholar]
  34. Li D., Bobrowicz P., Wilkinson H. H., Ebbole D. J. 2005; A mitogen-activated protein kinase pathway essential for mating and contributing to vegetative growth in Neurospora crassa . Genetics 170:1091–1104
    [Google Scholar]
  35. Liu F., Ng S. K., Lu Y., Low W., Lai J., Jedd G. 2008; Making two organelles from one: Woronin body biogenesis by peroxisomal protein sorting. J Cell Biol 180:325–339
    [Google Scholar]
  36. Lu B. C. K. 2006; Programmed cell death in fungi. In The Mycota: Growth, Differentiation and Sexuality pp 167–187 Edited by Esser K. Berlin, Heidelberg, New York: Springer;
    [Google Scholar]
  37. Ludovico P., Madeo F., Silva M. 2005; Yeast programmed cell death: an intricate puzzle. IUBMB Life 57:129–135
    [Google Scholar]
  38. Madeo F., Froehlich E., Ligr M., Grey M., Sigrist S. J., Wolf D. H., Froehlich K.-U. 1999; Oxygen stress: a regulator of apoptosis in yeast. J Cell Biol 145:757–767
    [Google Scholar]
  39. Madeo F., Herker E., Maldener C., Wissing S., Lächelt S., Herlan M., Fehr M., Lauber K., Sigrist S. J. 2002; A caspase-related protease regulates apoptosis in yeast. Mol Cell 9:911–917
    [Google Scholar]
  40. Marek S. M., Wu J., Glass N. L., Gilchrist D. G., Bostock R. M. 2003; Nuclear DNA degradation during heterokaryon incompatibility in Neurospora crassa . Fungal Genet Biol 40:126–137
    [Google Scholar]
  41. Margolin B. S., Freitag M., Selker E. U. 1997; Improved plasmids for gene targeting at the his-3 locus of Neurospora crassa by electroporation. Fungal Genet Newsl 44:34–36
    [Google Scholar]
  42. Markham P., Collinge A. J. 1987; Woronin bodies in filamentous fungi. FEMS Microbiol Rev 46:1–11
    [Google Scholar]
  43. Mazzoni C., Falcone C. 2008; Caspase-dependent apoptosis in yeast. Biochim Biophys Acta 17831320–1327
    [Google Scholar]
  44. Metzenberg R. L. 2004; Bird Medium: an alternative to Vogel Medium. Fungal Genet Newsl 51:19–20
    [Google Scholar]
  45. Michell R. H. 2008; Inositol derivatives: evolution and functions. Nat Rev Mol Cell Biol 9:151–161
    [Google Scholar]
  46. Modjtahedi N., Giordanetto F., Madeo F., Kroemer G. 2006; Apoptosis-inducing factor: vital and lethal. Trends Cell Biol 16:264–272
    [Google Scholar]
  47. Mousavi S. A. A., Robson G. D. 2004; Oxidative and amphotericin B-mediated cell death in the opportunistic pathogen Aspergillus fumigatus is associated with an apoptotic-like phenotype. Microbiology 150:1937–1945
    [Google Scholar]
  48. Mylyk O. M. 1975; Heterokaryon incompatibility genes in Neurospora crassa detected using duplication-producing chromosome rearrangements. Genetics 80:107–124
    [Google Scholar]
  49. Newhouse J. R., MacDonald W. L. 1991; The ultrastructure of hyphal anastomoses between vegetatively compatible and incompatible virulent and hypovirulent strains of Cryphonectria parasitica . Can J Bot 69:602–614
    [Google Scholar]
  50. Paoletti M., Clave C. 2007; The fungus-specific HET domain mediates programmed cell death in Podospora anserina . Eukaryot Cell 6:2001–2008
    [Google Scholar]
  51. Perkins D. D. 1984; Advantages of using the inactive-mating-type am1 strain as a helper component in heterokaryons. Fungal Genet Newsl 31:41–42
    [Google Scholar]
  52. Perkins D. D. 1988a; The use of duplication-generating rearrangements for studying heterokaryon incompatibility genes in Neurospora . Fungal Genet Newsl 35:44–46
    [Google Scholar]
  53. Perkins D. D. 1988b; Main features of vegetative incompatibility in Neurospora crassa . Fungal Genet Newsl 35:44–46
    [Google Scholar]
  54. Phillips A. J., Sudbery I., Ramsdale M. 2003; Apoptosis induced by environmental stresses and amphotericin B in Candida albicans . Proc Natl Acad Sci U S A 100:14327–14332
    [Google Scholar]
  55. Pinan-Lucarre B., Paoletti M., Dementhon K., Coulary-Salin B., Clave C. 2003; Autophagy is induced during cell death by incompatibility and is essential for differentiation in the filamentous fungus Podospora anserina . Mol Microbiol 47:321–333
    [Google Scholar]
  56. Pinan-Lucarre B., Balguerie A., Clave C. 2005; Accelerated cell death in Podospora autophagy mutants. Eukaryot Cell 4:1765–1774
    [Google Scholar]
  57. Ramsdale M. 2008; Programmed cell death in pathogenic fungi. Biochim Biophys Acta 17831369–1380
    [Google Scholar]
  58. Reape T. J., Molony E. M., McCabe P. F. 2008; Programmed cell death in plants: distinguishing between different modes. J Exp Bot 59:435–444
    [Google Scholar]
  59. Reed J. C. 2000 Apoptosis San Diego & London: Academic Press;
    [Google Scholar]
  60. Rong Y., Distelhorst C. W. 2008; Bcl-2 protein family members: versatile regulators of calcium signaling in cell survival and apoptosis. Annu Rev Physiol 70:73–91
    [Google Scholar]
  61. Ruepp A., Zollner A., Maier D., Albermann K., Hani J., Mokrejs M., Tetko I., Güldener U., Mannhaupt G. other authors 2004; The FunCat, a functional annotation scheme for systematic classification of proteins from whole genomes. Nucleic Acids Res 32:5539–5545
    [Google Scholar]
  62. Sadler A. J., Williams B. R. 2008; Interferon-inducible antiviral effectors. Nat Rev Immunol 8:559–568
    [Google Scholar]
  63. Sarkar S., Iyer G., Wu J., Glass N. L. 2002; Nonself recognition is mediated by HET-C heterocomplex formation during vegetative incompatibility. EMBO J 21:4841–4850
    [Google Scholar]
  64. Saupe S. J. 2000; Molecular genetics of heterokaryon incompatibility in filamentous ascomycetes. Microbiol Mol Biol Rev 64:489–502
    [Google Scholar]
  65. Saupe S. J., Glass N. L. 1997; Allelic specificity at the het-c heterokaryon incompatibility locus of Neurospora crassa is determined by a highly variable domain. Genetics 146:1299–1309
    [Google Scholar]
  66. Saupe S. J., Kuldau G. A., Smith M. L., Glass N. L. 1996; The product of the het-C heterokaryon incompatibility gene of Neurospora crassa has characteristics of a glycine-rich cell wall protein. Genetics 143:1589–1600
    [Google Scholar]
  67. Savoldi M., Malavazi I., Soriani F. M., Capellaro J. L., Kitamoto K., da Silva Ferreira M. E., Goldman M. H., Goldman G. H. 2008; Farnesol induces the transcriptional accumulation of the Aspergillus nidulans Apoptosis-Inducing Factor (AIF)-like mitochondrial oxidoreductase. Mol Microbiol 70:44–59
    [Google Scholar]
  68. Sbrana C., Nuti M., Giovannetti M. 2007; Self-anastomosing ability and vegetative incompatibility of Tuber borchii isolates. Mycorrhiza 17:667–675
    [Google Scholar]
  69. Schliebs W., Wurtz C., Kunau W.-H., Veenhuis M., Rottensteiner H. 2006; A eukaryote without catalase-containing microbodies: Neurospora crassa exhibits a unique cellular distribution of its four catalases. Eukaryot Cell 5:1490–1502
    [Google Scholar]
  70. Schrader M., Fahimi H. D. 2006; Peroxisomes and oxidative stress. Biochim Biophys Acta 17631755–1766
    [Google Scholar]
  71. Semighini C. P., Hornby J. M., Dumitru R., Nickerson K. W., Harris S. D. 2006; Farnesol-induced apoptosis in Aspergillus nidulans reveals a possible mechanism for antagonistic interactions between fungi. Mol Microbiol 59:753–764
    [Google Scholar]
  72. Severin F. F., Hyman A. A. 2002; Pheromone induces programmed cell death in S. cerevisiae . Curr Biol 12:R233–R235
    [Google Scholar]
  73. Silverman-Gavrila L. B., Lew R. R. 2002; An IP3-activated Ca2+ channel regulates fungal tip growth. J Cell Sci 115:5013–5025
    [Google Scholar]
  74. Strahl T., Thorner J. 2007; Synthesis and function of membrane phosphoinositides in budding yeast, Saccharomyces cerevisiae . Biochim Biophys Acta 1771:353–404
    [Google Scholar]
  75. Stridh H., Kimland M., Jones D. P., Orrenius S., Hampton M. B. 1998; Cytochrome c release and caspase activation in hydrogen peroxide- and tributyltin-induced apoptosis. FEBS Lett 429:351–355
    [Google Scholar]
  76. Suzuki C., Kawano M., Kashiwagi T., Arata Y., Kawasumi T., Kashiwagi Y. 2000; Lethal effect of the expression of a killer gene SMK1 in Saccharomyces cerevisiae . Protein Eng 13:73–76
    [Google Scholar]
  77. Takemoto D., Tanaka A., Scott B. 2007; NADPH oxidases in fungi: diverse roles of reactive oxygen species in fungal cellular differentiation. Fungal Genet Biol 44:1065–1076
    [Google Scholar]
  78. Tenney K., Hunt I., Sweigard J., Pounder J. I., McClain C., Bowman E. J., Bowman B. J. 2000; Hex-1, a gene unique to filamentous fungi, encodes the major protein of the Woronin body and functions as a plug for septal pores. Fungal Genet Biol 31:205–217
    [Google Scholar]
  79. Tian C., Kasuga T., Sachs M. S., Glass N. L. 2007; Transcriptional profiling of cross pathway control in Neurospora crassa and comparative analysis of the Gcn4 and CPC1 regulons. Eukaryot Cell 6:1018–1029
    [Google Scholar]
  80. Townsend J. P. 2003; Multifactorial experimental design and the transitivity of ratios with spotted DNA microarrays. BMC Genomics 4:41
    [Google Scholar]
  81. Townsend J. P. 2004; Resolution of large and small differences in gene expression using models for the Bayesian analysis of gene expression levels and spotted DNA microarrays. BMC Bioinformatics 5:54
    [Google Scholar]
  82. Townsend J. P., Hartl D. L. 2002; Bayesian analysis of gene expression levels: statistical quantification of relative mRNA level across multiple strains or treatments. Genome Biol 3:RESEARCH0071
    [Google Scholar]
  83. Vachova L., Palkova Z. 2007; Caspases in yeast apoptosis-like death: facts and artefacts. FEMS Yeast Res 7:12–21
    [Google Scholar]
  84. van Diepeningen A. D., Debets A. J. M., Hoekstra R. F. 1997; Heterokaryon incompatibility blocks virus transfer among natural isolates of black aspergilli. Curr Genet 32:209–217
    [Google Scholar]
  85. Vercammen D., Declercq W., Vandenabeele P., Van Breusegem F. 2007; Are metacaspases caspases?. J Cell Biol 179:375–380
    [Google Scholar]
  86. Videira A., Kasuga T., Tian C., Lemos C., Castro A., Glass N. L. 2009; Transcriptional analysis of the Neurospora crassa response to phytosphingosine reveals links to mitochondrial function. Microbiology 155:3134–3141
    [Google Scholar]
  87. Vogel H. J. 1956; A convenient growth medium for Neurospora . Microb Genet Bull 13:42–46
    [Google Scholar]
  88. Westergaard M., Mitchell H. K. 1947; Neurospora V. A synthetic medium favoring sexual reproduction. Am J Bot 34:573–577
    [Google Scholar]
  89. Wu J., Glass N. L. 2001; Identification of specificity determinants and generation of alleles with novel specificity at the het-c heterokaryon incompatibility locus of Neurospora crassa . Mol Cell Biol 21:1045–1057
    [Google Scholar]
  90. Wu J., Saupe S. J., Glass N. L. 1998; Evidence for balancing selection operating at the het-c heterokaryon incompatibility locus in a group of filamentous fungi. Proc Natl Acad Sci U S A 95:12398–12403
    [Google Scholar]
  91. Xiang Q., Glass N. L. 2002; Identification of vib-1, a locus involved in vegetative incompatibility mediated by het-c in Neurospora crassa . Genetics 162:89–101
    [Google Scholar]
  92. Zhang N.-N., Dudgeon D. D., Paliwal S., Levchenko A., Grote E., Cunningham K. W. 2006; Multiple signaling pathways regulate yeast cell death during the response to mating pheromones. Mol Biol Cell 17:3409–3422
    [Google Scholar]
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