#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

GPCR-mediated glucose sensing system regulates light-dependent fungal development and mycotoxin production


Autoři: Thaila Fernanda dos Reis aff001;  Laura Mellado aff001;  Jessica M. Lohmar aff003;  Lilian Pereira Silva aff001;  Jing-Jiang Zhou aff002;  Ana M. Calvo aff004;  Gustavo H. Goldman aff001;  Neil A. Brown aff005
Působiště autorů: Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, Ribeirão Preto, Brazil aff001;  Biointeractions and Crop Protection, Rothamsted Research, Hertfordshire, United Kingdom aff002;  Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Huaxi District, Guiyang, China aff003;  Department of Biological Sciences, Northern Illinois University, Illinois, United States of America aff004;  Department of Biology & Biochemistry, University of Bath, Claverton Down, Bath, United Kingdom aff005
Vyšlo v časopise: GPCR-mediated glucose sensing system regulates light-dependent fungal development and mycotoxin production. PLoS Genet 15(10): e32767. doi:10.1371/journal.pgen.1008419
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008419

Souhrn

Microorganisms sense environmental fluctuations in nutrients and light, coordinating their growth and development accordingly. Despite their critical roles in fungi, only a few G-protein coupled receptors (GPCRs) have been characterized. The Aspergillus nidulans genome encodes 86 putative GPCRs. Here, we characterise a carbon starvation-induced GPCR-mediated glucose sensing mechanism in A. nidulans. This includes two class V (gprH and gprI) and one class VII (gprM) GPCRs, which in response to glucose promote cAMP signalling, germination and hyphal growth, while negatively regulating sexual development in a light-dependent manner. We demonstrate that GprH regulates sexual development via influencing VeA activity, a key light-dependent regulator of fungal morphogenesis and secondary metabolism. We show that GprH and GprM are light-independent negative regulators of sterigmatocystin biosynthesis. Additionally, we reveal the epistatic interactions between the three GPCRs in regulating sexual development and sterigmatocystin production. In conclusion, GprH, GprM and GprI constitute a novel carbon starvation-induced glucose sensing mechanism that functions upstream of cAMP-PKA signalling to regulate fungal development and mycotoxin production.

Klíčová slova:

Fungal genetics – Fungal structure – G protein coupled receptors – Gene regulation – Glucose – Glucose signaling – Sexual differentiation – Aspergillus nidulans


Zdroje

1. Morris AJ, Malbon CC. Physiological regulation of G protein-linked signaling. Physiol Rev. 1999;79(4):1373–430. doi: 10.1152/physrev.1999.79.4.1373 10508237

2. Neves SR, Ram PT, Iyengar R. G protein pathways. Science. 2002;296(5573):1636–9. doi: 10.1126/science.1071550 12040175

3. Bolker M. Sex and crime: heterotrimeric G proteins in fungal mating and pathogenesis. Fungal Genet Biol. 1998;25(3):143–56. doi: 10.1006/fgbi.1998.1102 9917369

4. Han KH, Seo JA, Yu JH. A putative G protein-coupled receptor negatively controls sexual development in Aspergillus nidulans. Mol Microbiol. 2004;51(5):1333–45. doi: 10.1111/j.1365-2958.2003.03940.x 14982628

5. Lee N, D'Souza CA, Kronstad JW. Of smuts, blasts, mildews, and blights: cAMP signaling in phytopathogenic fungi. Annu Rev Phytopathol. 2003;41:399–427. doi: 10.1146/annurev.phyto.41.052002.095728 12651963

6. Lengeler KB, Davidson RC, D'souza C, Harashima T, Shen WC, Wang P, et al. Signal transduction cascades regulating fungal development and virulence. Microbiol Mol Biol Rev. 2000;64(4):746–85. doi: 10.1128/mmbr.64.4.746-785.2000 11104818

7. Yu JH, Keller N. Regulation of secondary metabolism in filamentous fungi. Annu Rev Phytopathol. 2005;43:437–58. doi: 10.1146/annurev.phyto.43.040204.140214 16078891

8. Pontecorvo G, Roper JA, Hemmons LM, MacDonald KD, Bufton AW. The genetics of Aspergillus nidulans. Adv Genet. 1953;5:141–238. 13040135

9. Paulussen C, Hallsworth JE, Alvarez-Perez S, Nierman WC, Hamill PG, Blain D, et al. Ecology of aspergillosis: insights into the pathogenic potency of Aspergillus fumigatus and some other Aspergillus species. Microb Biotechnol. 2017;10(2):296–322. doi: 10.1111/1751-7915.12367 27273822

10. Li L, Wright SJ, Krystofova S, Park G, Borkovich KA. Heterotrimeric G protein signaling in filamentous fungi. Annu Rev Microbiol. 2007;61:423–52. doi: 10.1146/annurev.micro.61.080706.093432 17506673

11. Brown NA, Schrevens S, van Dijck P, Goldman GH. Fungal G-protein-coupled receptors: mediators of pathogenesis and targets for disease control. Nature Microbiology. 2018;3(4):402–14. doi: 10.1038/s41564-018-0127-5 29588541

12. DeZwaan TM, Carroll AM, Valent B, Sweigard JA. Magnaporthe grisea Pth11p is a novel plasma membrane protein that mediates appressorium differentiation in response to inductive substrate cues. Plant Cell. 1999;11(10):2013–30. doi: 10.1105/tpc.11.10.2013 10521529

13. Dilks T, Halsey K, De Vos RP, Hammond-Kosack KE, Brown NA. Non-canonical fungal G-protein coupled receptors promote Fusarium head blight on wheat. Plos Pathogens. 2019;15(4).

14. Hoffmann B, Wanke C, Lapaglia SK, Braus GH. c-Jun and RACK1 homologues regulate a control point for sexual development in Aspergillus nidulans. Mol Microbiol. 2000;37(1):28–41. doi: 10.1046/j.1365-2958.2000.01954.x 10931303

15. Seo JA, Han KH, Yu JH. The gprA and gprB genes encode putative G protein-coupled receptors required for self-fertilization in Aspergillus nidulans. Mol Microbiol. 2004;53(6):1611–23. doi: 10.1111/j.1365-2958.2004.04232.x 15341643

16. Brown NA, Dos Reis TF, Ries LN, Caldana C, Mah JH, Yu JH, et al. G-protein coupled receptor-mediated nutrient sensing and developmental control in Aspergillus nidulans. Mol Microbiol. 2015;98(3):420–39. doi: 10.1111/mmi.13135 26179439

17. Stinnett SM, Espeso EA, Cobeno L, Araujo-Bazan L, Calvo AM. Aspergillus nidulans VeA subcellular localization is dependent on the importin alpha carrier and on light. Mol Microbiol. 2007;63(1):242–55. doi: 10.1111/j.1365-2958.2006.05506.x 17163983

18. Purschwitz J, Muller S, Kastner C, Schoser M, Haas H, Espeso EA, et al. Functional and physical interaction of blue- and red-light sensors in Aspergillus nidulans. Curr Biol. 2008;18(4):255–9. doi: 10.1016/j.cub.2008.01.061 18291652

19. Bayram O, Braus GH, Fischer R, Rodriguez-Romero J. Spotlight on Aspergillus nidulans photosensory systems. Fungal Genet Biol. 2010;47(11):900–8. doi: 10.1016/j.fgb.2010.05.008 20573560

20. Calvo AM, Lohmar JM, Ibarra B, Satterlee T. Velvet regulation of fungal development. J Wedland. Springer International Publishing.; 2016. p. 475–97.

21. Mooney JL, Hassett DE, Yager LN. Genetic analysis of suppressors of the veA1 mutation in Aspergillus nidulans. Genetics. 1990;126(4):869–74. 2076818

22. Mooney JL, Yager LN. Light is required for conidiation in Aspergillus nidulans. Genes Dev. 1990;4(9):1473–82. doi: 10.1101/gad.4.9.1473 2253875

23. Dasgupta A, Fuller KK, Dunlap JC, Loros JJ. Seeing the world differently: variability in the photosensory mechanisms of two model fungi. Environ Microbiol. 2016;18(1):5–20. doi: 10.1111/1462-2920.13055 26373782

24. Bayram O, Krappmann S, Ni M, Bok JW, Helmstaedt K, Valerius O, et al. VelB/VeA/LaeA complex coordinates light signal with fungal development and secondary metabolism. Science. 2008;320(5882):1504–6. doi: 10.1126/science.1155888 18556559

25. Bayram O, Braus GH. Coordination of secondary metabolism and development in fungi: the velvet family of regulatory proteins. FEMS Microbiol Rev. 2012;36(1):1–24. doi: 10.1111/j.1574-6976.2011.00285.x 21658084

26. Calvo AM, Lohmar JM, Ibarra B, Satterlee T. Velvet Regulation of Fungal Development. In: Wendland J, editor. Growth, Differentiation and Sexuality, 3rd Edition. Mycota-A Comprehensive Treatise on Fungi as Experimental Systems for Basic and Applied Research. 12016. p. 475–97.

27. Calvo AM, Wilson RA, Bok JW, Keller NP. Relationship between secondary metabolism and fungal development. Microbiol Mol Biol Rev. 2002;66(3):447–59, table. doi: 10.1128/MMBR.66.3.447-459.2002 12208999

28. Yu JH, Leonard TJ. Sterigmatocystin biosynthesis in Aspergillus nidulans requires a novel type I polyketide synthase. J Bacteriol. 1995;177(16):4792–800. doi: 10.1128/jb.177.16.4792-4800.1995 7642507

29. Wu F, Groopman JD, Pestka JJ. Public health impacts of foodborne mycotoxins. Annu Rev Food Sci Technol. 2014;5:351–72. doi: 10.1146/annurev-food-030713-092431 24422587

30. Jiang X, Wang J, Xing L, Shen H, Lian W, Yi L, et al. Sterigmatocystin-induced checkpoint adaptation depends on Chk1 in immortalized human gastric epithelial cells in vitro. Arch Toxicol. 2017;91(1):259–70. doi: 10.1007/s00204-016-1682-2 26914363

31. Fernandes M, Keller NP, Adams TH. Sequence-specific binding by Aspergillus nidulans AflR, a C6 zinc cluster protein regulating mycotoxin biosynthesis. Mol Microbiol. 1998;28(6):1355–65. doi: 10.1046/j.1365-2958.1998.00907.x 9680223

32. Shimizu K, Keller NP. Genetic involvement of a cAMP-dependent protein kinase in a G protein signaling pathway regulating morphological and chemical transitions in Aspergillus nidulans. Genetics. 2001;157(2):591–600. 11156981

33. Bok JW, Keller NP. LaeA, a regulator of secondary metabolism in Aspergillus spp. Eukaryot Cell. 2004;3(2):527–35. doi: 10.1128/EC.3.2.527-535.2004 15075281

34. Atoui A, Kastner C, Larey CM, Thokala R, Etxebeste O, Espeso EA, et al. Cross-talk between light and glucose regulation controls toxin production and morphogenesis in Aspergillus nidulans. Fungal Genet Biol. 2010;47(12):962–72. doi: 10.1016/j.fgb.2010.08.007 20816830

35. Kato N, Brooks W, Calvo AM. The expression of sterigmatocystin and penicillin genes in Aspergillus nidulans is controlled by veA, a gene required for sexual development. Eukaryot Cell. 2003;2(6):1178–86. doi: 10.1128/EC.2.6.1178-1186.2003 14665453

36. Bayram O, Bayram OS, Ahmed YL, Maruyama J, Valerius O, Rizzoli SO, et al. The Aspergillus nidulans MAPK module AnSte11-Ste50-Ste7-Fus3 controls development and secondary metabolism. PLoS Genet. 2012;8(7):e1002816. doi: 10.1371/journal.pgen.1002816 22829779

37. Klein PS, Sun TJ, Saxe CL, III, Kimmel AR, Johnson RL, Devreotes PN. A chemoattractant receptor controls development in Dictyostelium discoideum. Science. 1988;241(4872):1467–72. doi: 10.1126/science.3047871 3047871

38. Krohn NG, Brown NA, Colabardini AC, Reis T, Savoldi M, Dinamarco TM, et al. The Aspergillus nidulans ATM kinase regulates mitochondrial function, glucose uptake and the carbon starvation response. G3 (Bethesda). 2014;4(1):49–62.

39. Stajich JE, Harris T, Brunk BP, Brestelli J, Fischer S, Harb OS, et al. FungiDB: an integrated functional genomics database for fungi. Nucleic Acids Research. 2012;40(D1):D675–D81.

40. Ni M, Rierson S, Seo JA, Yu JH. The pkaB gene encoding the secondary protein kinase A catalytic subunit has a synthetic lethal interaction with pkaA and plays overlapping and opposite roles in Aspergillus nidulans. Eukaryot Cell. 2005;4(8):1465–76. doi: 10.1128/EC.4.8.1465-1476.2005 16087751

41. Han KH, Lee DB, Kim JH, Kim MS, Han KY, Kim WS, et al. Environmental factors affecting development of Aspergillus nidulans. J Microbiol. 2003;41:34–40.

42. Han DM, Han YJ, Chae KS, Jahng KY, Y.H. L. Effects of various carbon sources on the development of Aspergillus nidulans with velA~ or velAl allele. Kor J Mycol. 1994;22:332.

43. Krijgsheld P, Bleichrodt R, van Veluw GJ, Wang F, Muller WH, Dijksterhuis J, et al. Development in Aspergillus. Stud Mycol. 2013;74(1):1–29. doi: 10.3114/sim0006 23450714

44. Yager LN. Early developmental events during asexual and sexual sporulation in Aspergillus nidulans. Biotechnology. 1992;23:19–41. 1504597

45. Palmer JM, Theisen JM, Duran RM, Grayburn WS, Calvo AM, Keller NP. Secondary metabolism and development is mediated by LlmF control of VeA subcellular localization in Aspergillus nidulans. PLoS Genet. 2013;9(1):e1003193. doi: 10.1371/journal.pgen.1003193 23341778

46. Champe SP, M.B. Kurtz, L.N. Yager, N.J. Butnick, D.E. Axelrod. Spore formation in Aspergillus nidulans: Competence and other developmental processes. The fungal spore: Morphogenetic controls,. New York, N.Y., USA: Academic Press, Inc; 1981. p. 63–91.

47. Calvo AM. The VeA regulatory system and its role in morphological and chemical development in fungi. Fungal Genet Biol. 2008;45(7):1053–61. doi: 10.1016/j.fgb.2008.03.014 18457967

48. Brakhage AA, Browne P, Turner G. Analysis of the regulation of penicillin biosynthesis in Aspergillus nidulans by targeted disruption of the acvA gene. Mol Gen Genet. 1994;242(1):57–64. doi: 10.1007/bf00277348 8277946

49. Van Dijck P, Brown NA, Goldman GH, Rutherford J, Xue CY, Van Zeebroeck G. Nutrient Sensing at the Plasma Membrane of Fungal Cells. Microbiology Spectrum. 2017;5(2).

50. de Souza WR, Morais ER, Krohn NG, Savoldi M, Goldman MHS, Rodrigues F, et al. Identification of metabolic pathways influenced by the G-Protein coupled receptors GprB and GprD in Aspergillus nidulans. PLoS One. 2013;8:1–13.

51. Pawson T, Scott JD. Protein phosphorylation in signaling-50 years and counting. Trends Biochem Sci 30: 286–290. doi: 10.1016/j.tibs.2005.04.013 15950870

52. Blumenstein A, Vienken K, Tasler R, Purschwitz J, Veith D, Frankenberg-Dinkel N, et al. The Aspergillus nidulans phytochrome FphA represses sexual development in red light. Curr Biol. 2005;15(20):1833–8. doi: 10.1016/j.cub.2005.08.061 16243030

53. Kim H, Han K, Kim K, Han D, Jahng K, Chae K. The veA gene activates sexual development in Aspergillus nidulans. Fungal Genet Biol. 2002;37(1):72–80. 12223191

54. Tag A, Hicks J, Garifullina G, Ake C Jr., Phillips TD, Beremand M, et al. G-protein signalling mediates differential production of toxic secondary metabolites. Mol Microbiol. 2000;38(3):658–65. doi: 10.1046/j.1365-2958.2000.02166.x 11069688

55. Seo JA, Yu JH. The phosducin-like protein PhnA is required for Gbetagamma-mediated signaling for vegetative growth, developmental control, and toxin biosynthesis in Aspergillus nidulans. Eukaryot Cell. 2006;5(2):400–10. doi: 10.1128/EC.5.2.400-410.2006 16467480

56. Tilburn J, Scazzocchio C, Taylor GG, Zabicky-Zissman JH, Lockington RA, Davies RW. Transformation by integration in Aspergillus nidulans. Gene. 1983;26(2–3):205–21. doi: 10.1016/0378-1119(83)90191-9 6368319

57. Todd RB, Davis MA, Hynes MJ. Genetic manipulation of Aspergillus nidulans: meiotic progeny for genetic analysis and strain construction. Nat Protoc. 2007;2(4):811–21. doi: 10.1038/nprot.2007.112 17446881

58. Nayak T, Szewczyk E, Oakley CE, Osmani A, Ukil L, Murray SL, et al. A versatile and efficient gene-targeting system for Aspergillus nidulans. Genetics. 2006;172(3):1557–66. doi: 10.1534/genetics.105.052563 16387870

59. Schiestl RH, Gietz RD. High-efficiency transformation of intact yeast-cells using single stranded nucleic-acids as a carrier. Current Genetics. 1989;16(5–6):339–46. doi: 10.1007/bf00340712 2692852

60. Osmani SA, May GS, Morris NR. Regulation of the messenger-RNA levels of nimA, a gene required for the G2-m transition in Aspergillus nidulans. Journal of Cell Biology. 1987;104(6):1495–504. doi: 10.1083/jcb.104.6.1495 3294854

61. Boeke JD, LaCroute F, Fink GR. A positive selection for mutants lacking orotidine-5'-phosphate decarboxylase activity in yeast: 5-fluoro-orotic acid resistance. Mol Gen Genet. 1984;197(2):345–6. doi: 10.1007/bf00330984 6394957

62. de Assis LJ, Ries LN, Savoldi M, Dos Reis TF, Brown NA, Goldman GH. Aspergillus nidulans protein kinase A plays an important role in cellulase production. Biotechnol Biofuels. 2015;8:213. doi: 10.1186/s13068-015-0401-1 26690721

63. Semighini CP, Marins M, Goldman MH, Goldman GH. Quantitative analysis of the relative transcript levels of ABC transporter Atr genes in Aspergillus nidulans by real-time reverse transcription-PCR assay. Appl Environ Microbiol. 2002;68(3):1351–7. doi: 10.1128/AEM.68.3.1351-1357.2002 11872487

64. Rauscher S, Pacher S, Hedtke M, Kniemeyer O, Fischer R. A phosphorylation code of the Aspergillus nidulans global regulator VelvetA (VeA) determines specific functions. Molecular Microbiology. 2016;99(5):909–24. doi: 10.1111/mmi.13275 26564476

65. Ramamoorthy V, Dhingra S, Kincaid A, Shantappa S, Feng X, Calvo AM. The putative C2H2 transcription factor MtfA is a novel regulator of secondary metabolism and morphogenesis in Aspergillus nidulans. PLoS One. 2013;8(9):e74122. doi: 10.1371/journal.pone.0074122 24066102

66. Palmer JM, Perrin RM, Dagenais TRT, Keller NP. H3K9 Methylation Regulates Growth and Development in Aspergillus fumigatus. Eukaryotic Cell. 2008;7(12):2052–60. doi: 10.1128/EC.00224-08 18849468

Štítky
Genetika Reprodukční medicína

Článek vyšel v časopise

PLOS Genetics


2019 Číslo 10
Nejčtenější tento týden
Nejčtenější v tomto čísle
Kurzy

Zvyšte si kvalifikaci online z pohodlí domova

plice
INSIGHTS from European Respiratory Congress
nový kurz

Současné pohledy na riziko v parodontologii
Autoři: MUDr. Ladislav Korábek, CSc., MBA

Svět praktické medicíny 3/2024 (znalostní test z časopisu)

Kardiologické projevy hypereozinofilií
Autoři: prof. MUDr. Petr Němec, Ph.D.

Střevní příprava před kolonoskopií
Autoři: MUDr. Klára Kmochová, Ph.D.

Všechny kurzy
Kurzy Podcasty Doporučená témata Časopisy
Přihlášení
Zapomenuté heslo

Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se

#ADS_BOTTOM_SCRIPTS#