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The High Osmolarity Glycerol Mitogen-Activated Protein Kinase regulates glucose catabolite repression in filamentous fungi


Autoři: Leandro José de Assis aff001;  Lilian Pereira Silva aff001;  Li Liu aff002;  Kerstin Schmitt aff002;  Oliver Valerius aff002;  Gerhard H. Braus aff002;  Laure Nicolas Annick Ries aff003;  Gustavo Henrique Goldman aff001
Působiště autorů: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Bloco Q, Universidade de São Paulo, Brazil aff001;  Department of Molecular Microbiology and Genetics and Goettingen Center for Molecular Biosciences (GZMB), University of Goettingen, Goettingen, Germany aff002;  Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Brazil aff003;  Institute for Advanced Study, Technical University of Munich, Garching, Germany aff004
Vyšlo v časopise: The High Osmolarity Glycerol Mitogen-Activated Protein Kinase regulates glucose catabolite repression in filamentous fungi. PLoS Genet 16(8): e32767. doi:10.1371/journal.pgen.1008996
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008996

Souhrn

The utilization of different carbon sources in filamentous fungi underlies a complex regulatory network governed by signaling events of different protein kinase pathways, including the high osmolarity glycerol (HOG) and protein kinase A (PKA) pathways. This work unraveled cross-talk events between these pathways in governing the utilization of preferred (glucose) and non-preferred (xylan, xylose) carbon sources in the reference fungus Aspergillus nidulans. An initial screening of a library of 103 non-essential protein kinase (NPK) deletion strains identified several mitogen-activated protein kinases (MAPKs) to be important for carbon catabolite repression (CCR). We selected the MAPKs Ste7, MpkB, and PbsA for further characterization and show that they are pivotal for HOG pathway activation, PKA activity, CCR via regulation of CreA cellular localization and protein accumulation, as well as for hydrolytic enzyme secretion. Protein-protein interaction studies show that Ste7, MpkB, and PbsA are part of the same protein complex that regulates CreA cellular localization in the presence of xylan and that this complex dissociates upon the addition of glucose, thus allowing CCR to proceed. Glycogen synthase kinase (GSK) A was also identified as part of this protein complex and shown to potentially phosphorylate two serine residues of the HOG MAPKK PbsA. This work shows that carbon source utilization is subject to cross-talk regulation by protein kinases of different signaling pathways. Furthermore, this study provides a model where the correct integration of PKA, HOG, and GSK signaling events are required for the utilization of different carbon sources.

Klíčová slova:

Aspergillus nidulans – Enzyme regulation – Glucose – Glucose signaling – MAPK signaling cascades – Phosphorylation – Protein kinases – Xylose


Zdroje

1. Brown NA, de Gouvea PF, Krohn NG, Savoldi M, Goldman GH. Functional characterisation of the non-essential protein kinases and phosphatases regulating Aspergillus nidulans hydrolytic enzyme production. Biotechnol Biofuels. 2013;6: 91. doi: 10.1186/1754-6834-6-91 23800192

2. Tamayo EN, Villanueva A a., Hasper A, Graaff LHD, Ramón D, Orejas M. CreA mediates repression of the regulatory gene xlnR which controls the production of xylanolytic enzymes in Aspergillus nidulans. Fung Gen Biol. 2008;45: 984–993. doi: 10.1016/j.fgb.2008.03.002 18420433

3. Beattie SR, Mark KMKK, Thammahong A, Ries LNA, Dhingra S, Caffrey-Carr AK, et al. Filamentous fungal carbon catabolite repression supports metabolic plasticity and stress responses essential for disease progression. Krysan DJ, editor. PloS Pathog. 2017;13: e1006340. doi: 10.1371/journal.ppat.1006340 28423062

4. Pe A, Orejas M, Cabe APMAC, Kumar S, Ramo D, MacCabe AP, et al. The Wide-Domain Carbon Catabolite Repressor CreA Indirectly Controls Expression of the Aspergillus nidulans xlnB Gene, Encoding the Acidic Endo-β- (1, 4) -Xylanase. J Bacteriol. 2001;183: 1517–1523. doi: 10.1128/JB.183.5.1517-1523.2001 11160081

5. van der Veen P, Ruijter JGG, Visser J. An extreme creA mutation in Aspergillus nidulans has severe effects on D-glucose utilization. Microbiology. 1995;141: 2301–2306. doi: 10.1099/13500872-141-9-2301 7496542

6. Cupertino FB, Virgilio S, Freitas FZ, Candido T de S, Bertolini MC. Regulation of glycogen metabolism by the CRE-1, RCO-1 and RCM-1 proteins in Neurospora crassa. The role of CRE-1 as the central transcriptional regulator. Fung Gen Biol. Elsevier Inc.; 2015;77: 82–94. doi: 10.1016/j.fgb.2015.03.011 25889113

7. de Assis LJ, Ulas M, Ries LNA, El Ramli NAM, Sarikaya-Bayram O, Braus GH, et al. Regulation of Aspergillus nidulans CreA-Mediated Catabolite Repression by the F-Box Proteins Fbx23 and Fbx47. Yu J-H, Bahn Y-S, editors. MBio. 2018;9: e00840–18. doi: 10.1128/mBio.00840-18 29921666

8. Strauss J, Horvath HK, Abdallah BM, Kindermann J, Mach RL, Kubicek CP. The function of CreA, the carbon catabolite repressor of Aspergillus nidulans, is regulated at the transcriptional and post-transcriptional level. Mol Microbiol. 1999;32: 169–178. doi: 10.1046/j.1365-2958.1999.01341.x 10216870

9. Alam MA, Kamlangdee N, Kelly JM. The CreB deubiquitinating enzyme does not directly target the CreA repressor protein in Aspergillus nidulans. Curr Genet. Springer Berlin Heidelberg; 2016; doi: 10.1007/s00294-016-0643-x 27589970

10. Cziferszky A, Mach RL, Kubicek CP. Phosphorylation Positively Regulates DNA Binding of the Carbon Catabolite Repressor Cre1 of Hypocrea jecorina (Trichoderma reesei) *. J Biol Chem. 2002;277: 14688–14694. doi: 10.1074/jbc.M200744200 11850429

11. Ribeiro LFC, Chelius C, Boppidi KR, Naik NS, Hossain S, Ramsey JJJ, et al. Comprehensive Analysis of Aspergillus nidulans PKA Phosphorylome Identifies a Novel Mode of CreA Regulation. Lin X, editor. MBio. American Society for Microbiology; 2019;10. doi: 10.1128/mBio.02825-18 31040248

12. Hedbacker K, Carlson M. SNF1/AMPK pathways in yeast. Front Biosci. 2008;13: 2408. doi: 10.2741/2854 17981722

13. McCartney RR, Schmidt MC. Regulation of Snf1 Kinase. Activation requires phosphorylation of threonine 210 by an upstream kinase as well as a distinct step mediated by the Snf4 subunit. J Biol Chem. 2001;276: 36460–36466. doi: 10.1074/jbc.M104418200 11486005

14. De Vit MJ, Waddle Ja, Johnston M. Regulated nuclear translocation of the Mig1 glucose repressor. Mol Biol Cell. 1997;8: 1603–1618. doi: 10.1091/mbc.8.8.1603 9285828

15. de Assis LJ, Ries LNA, Savoldi M, dos Reis TF, Brown NA, Goldman GH. Aspergillus nidulans protein kinase A plays an important role in cellulase production. Biotechnol Biofuels. BioMed Central; 2015;8: 213–223. doi: 10.1186/s13068-015-0401-1 26690721

16. Gancedo JM. The early steps of glucose signalling in yeast. FEMS Microb Rev. 2008;32: 673–704. doi: 10.1111/j.1574-6976.2008.00117.x 18559076

17. Flipphi M, van de Vondervoort PJII, Ruijter GJGG, Visser J, Arst HN, Felenbok B. Onset of carbon catabolite repression in Aspergillus nidulans. Parallel involvement of hexokinase and glucokinase in sugar signaling. J Biol Chem. 2003;278: 11849–11857. doi: 10.1074/jbc.M209443200 12519784

18. Brown NA, Ries LNA, Goldman GH. How nutritional status signalling coordinates metabolism and lignocellulolytic enzyme secretion. Fung Gen Biol. 2014;72: 48–63. doi: 10.1016/j.fgb.2014.06.012 25011009

19. Krijgsheld P, Bleichrodt R, Veluw GJ Van, Wang F, Dijksterhuis J. Development in Aspergillus. Stud Mycol. 2012;74: 1–29. doi: 10.3114/sim0006 23450714

20. Cho Y, Cramer RA Jr., Kim K-H, Davis J, Mitchell TK, Figuli P, et al. The Fus3/Kss1 MAP kinase homolog Amk1 regulates the expression of genes encoding hydrolytic enzymes in Alternaria brassicicola☆. Fung Gen Biol. 2007;44: 543–553. doi: 10.1016/j.fgb.2006.11.015 17280842

21. Lev S, Horwitz BA. A mitogen-activated protein kinase pathway modulates the expression of two cellulase genes in Cochliobolus heterostrophus during plant infection. Plant Cell. 2003; doi: 10.1105/tpc.010546.was

22. Huberman LB, Coradetti ST, Glass NL. Network of nutrient-sensing pathways and a conserved kinase cascade integrate osmolarity and carbon sensing in Neurospora crassa. Proc Natl Acad Sci. 2017;114: E8665–E8674. doi: 10.1073/pnas.1707713114 28973881

23. Wang M, Zhang M, Li L, Dong Y, Jiang Y, Liu K, et al. Role of Trichoderma reesei mitogen-activated protein kinases (MAPKs) in cellulase formation. Biotechnol Biofuels. BioMed Central; 2017;10: 99. doi: 10.1186/s13068-017-0789-x 28435444

24. Wang M, Zhao Q, Yang J, Jiang B, Wang F, Liu K, et al. A Mitogen-Activated Protein Kinase Tmk3 Participates in High Osmolarity Resistance, Cell Wall Integrity Maintenance and Cellulase Production Regulation in Trichoderma reesei. Harris S, editor. PLoS One. 2013;8: e72189. doi: 10.1371/journal.pone.0072189 23991059

25. Waltereit R, Weller M. Signaling from cAMP/PKA to MAPK and Synaptic Plasticity. Mol Neurobiol. 2003;27: 99–106. doi: 10.1385/MN:27:1:99 12668903

26. Vogt Weisenhorn DM, Roback LJ, Kwon JH, Wainer BH. Coupling of cAMP/PKA and MAPK Signaling in Neuronal Cells Is Dependent on Developmental Stage. Exp Neurol. 2001;169: 44–55. doi: 10.1006/exnr.2001.7651 11312557

27. Nelson DL, Cox MM. Lehninger Principles of Biochemistry 6th ed. sixth edit. Freeman WH, editor. Book. New York: Palgrave Macmillan; 2014.

28. de Assis LJ, Manfiolli A, Mattos E, Fabri JHTM, Malavazi I, Jacobsen ID, et al. Protein Kinase A and High-Osmolarity Glycerol Response Pathways Cooperatively Control Cell Wall Carbohydrate Mobilization in Aspergillus fumigatus. Fischer R, editor. MBio. 2018;9: e01952–18. doi: 10.1128/mBio.01952-18 30538182

29. Freitas FZ, de Paula RM, Barbosa LCB, Terenzi HF, Bertolini MC. cAMP signaling pathway controls glycogen metabolism in Neurospora crassa by regulating the glycogen synthase gene expression and phosphorylation. Fung Gen Biol. Elsevier Inc.; 2010;47: 43–52. doi: 10.1016/j.fgb.2009.10.011 19883780

30. De Souza CP, Hashmi SB, Osmani AH, Andrews P, Ringelberg CS, Dunlap JC, et al. Functional analysis of the Aspergillus nidulans kinome. PLoS One. 2013;8: e58008. doi: 10.1371/journal.pone.0058008 23505451

31. Ries LNA, Beattie SR, Espeso EA, Cramer RA, Goldman GH. Diverse Regulation of the CreA Carbon Catabolite Repressor in Aspergillus nidulans. Genetics. 2016;203: 335–352. doi: 10.1534/genetics.116.187872 27017621

32. O’Donnell a. F, McCartney RR, Chandrashekarappa DG, Zhang BB, Thorner J, Schmidt MC. 2-Deoxyglucose impairs yeast growth by stimulating Snf1-regulated and -arrestin-mediated trafficking of hexose transporters 1 and 3 in Saccharomyces cerevisiae. Mol Cell Biol. 2014;35: 939–955. doi: 10.1128/MCB.01183-14 25547292

33. Hicks J, Lockington RA, Strauss J, Dieringer D, Kubicek CP, Kelly J, et al. RcoA has pleiotropic effects on Aspergillus nidulans cellular development. Mol Microbiol. 2001;39: 1482–1493. doi: 10.1046/j.1365-2958.2001.02332.x 11260466

34. Shroff RA, Lockington RA, Kelly JM. Analysis of mutations in the creA gene involved in carbon catabolite repression in Aspergillus nidulans. Can J Microbiol. 1996;42: 950–959. doi: 10.1139/m96-122 8864218

35. Ries LNA, Steenwyk JL, de Castro PA, de Lima PBA, Almeida F, de Assis LJ, et al. Nutritional Heterogeneity Among Aspergillus fumigatus Strains Has Consequences for Virulence in a Strain- and Host-Dependent Manner. Front Microbiol. 2019;10: 1–20. doi: 10.3389/fmicb.2019.00001

36. Uchida K, Kanematsu M, Sakai K, Matsuda T, Hattori N, Mizuno Y, et al. Protein-bound acrolein: Potential markers for oxidative stress. Proc Natl Acad Sci. 1998;95: 4882–4887. doi: 10.1073/pnas.95.9.4882 9560197

37. Kwolek-Mirek M, Bednarska S, Bartosz G, Biliński T. Acrolein toxicity involves oxidative stress caused by glutathione depletion in the yeast Saccharomyces cerevisiae. Cell Biol Toxicol. 2009;25: 363–378. doi: 10.1007/s10565-008-9090-x 18563599

38. Kwolek-Mirek M, Zadrąg-Tęcza R, Bednarska S, Bartosz G. Acrolein-Induced Oxidative Stress and Cell Death Exhibiting Features of Apoptosis in the Yeast Saccharomyces cerevisiae Deficient in SOD1. Cell Biochem Biophys. 2015;71: 1525–1536. doi: 10.1007/s12013-014-0376-8 25395196

39. von Zeska Kress MR, Harting R, Bayram Ö, Christmann M, Irmer H, Valerius O, et al. The COP9 signalosome counteracts the accumulation of cullin SCF ubiquitin E3 RING ligases during fungal development. Mol Microbiol. 2012;83: 1162–77. doi: 10.1111/j.1365-2958.2012.07999.x 22329854

40. Elorza MV, Arst HN. Sorbose resistant mutants of Aspergillus nidulans. Mol Gener Gen. 1971;111: 185–193. doi: 10.1007/BF00267792 5564468

41. Vishwanatha A, D’Souza CJM. Multifaceted effects of antimetabolite and anticancer drug, 2-deoxyglucose on eukaryotic cancer models budding and fission yeast. IUBMB Life. 2017;69: 137–147. doi: 10.1002/iub.1599 28093891

42. Pereira Silva L, Alves de Castro P, dos Reis TF, Paziani MH, Von Zeska Kress MR, Riaño-Pachón DM, et al. Genome-wide transcriptome analysis of Aspergillus fumigatus exposed to osmotic stress reveals regulators of osmotic and cell wall stresses that are SakAHOG1 and MpkC dependent. Cell Microbiol. 2017;19: 1–21. doi: 10.1111/cmi.12681 27706915

43. Lara-Rojas F, Sánchez O, Kawasaki L, Aguirre J. Aspergillus nidulans transcription factor AtfA interacts with the MAPK SakA to regulate general stress responses, development and spore functions. Mol Microbiol. 2011;80: 436–454. doi: 10.1111/j.1365-2958.2011.07581.x 21320182

44. Yu Z, Armant O, Fischer R. Fungi use the SakA (HogA) pathway for phytochrome-dependent light signalling. Nat Microbiol. Nature Publishing Group; 2016; 16019. doi: 10.1038/nmicrobiol.2016.19 27572639

45. Idnurm A, Bahn YS. Fungal physiology: Red light plugs into MAPK pathway. Nat Microbiol. Macmillan Publishers Limited; 2016;1: 1–2. doi: 10.1038/nmicrobiol.2016.52 27572650

46. Cheung WD, Hart GW. AMP-activated Protein Kinase and p38 MAPK Activate O -GlcNAcylation of Neuronal Proteins during Glucose Deprivation. J Biol Chem. 2008;283: 13009–13020. doi: 10.1074/jbc.M801222200 18353774

47. Karunanithi S, Cullen PJ. The Filamentous Growth MAPK Pathway Responds to Glucose Starvation Through in Saccharomyces cerevisiae. Genetics. 2012;192: 869–887. doi: 10.1534/genetics.112.142661 22904036

48. Brewster JL, Gustin MC. Hog1: 20 years of discovery and impact. Sci Signal. 2014;7: re7–re7. doi: 10.1126/scisignal.2005458 25227612

49. de Paula RG, Antoniêto ACC, Carraro CB, Lopes DCB, Persinoti GF, Peres NTA, et al. The Duality of the MAPK Signaling Pathway in the Control of Metabolic Processes and Cellulase Production in Trichoderma reesei. Sci Rep. 2018;8: 14931. doi: 10.1038/s41598-018-33383-1 30297963

50. Sebastián-Pérez V, Manoli M-T, Pérez DI, Gil C, Mellado E, Martínez A, et al. New applications for known drugs: Human glycogen synthase kinase 3 inhibitors as modulators of Aspergillus fumigatus growth. Euro J Med Chem. Elsevier Ltd; 2016;116: 281–289. doi: 10.1016/j.ejmech.2016.03.035 27131621

51. Wang M, Dong Y, Zhao Q, Wang F, Liu K, Jiang B, et al. Identification of the role of a MAP kinase Tmk2 in Hypocrea jecorina (Trichoderma reesei). Sci Rep. 2014;4: 6732. doi: 10.1038/srep06732 25339247

52. Blom N, Gammeltoft S, Brunak S. Sequence and structure-based prediction of eukaryotic protein phosphorylation sites. J Mol Biol. 1999;294: 1351–1362. doi: 10.1006/jmbi.1999.3310 10600390

53. Blom N, Sicheritz-Pontén T, Gupta R, Gammeltoft S, Brunak S. Prediction of post-translational glycosylation and phosphorylation of proteins from the amino acid sequence. Proteomics. 2004;4: 1633–1649. doi: 10.1002/pmic.200300771 15174133

54. Murakami Y, Tatebayashi K, Saito H. Two Adjacent Docking Sites in the Yeast Hog1 Mitogen-Activated Protein (MAP) Kinase Differentially Interact with the Pbs2 MAP Kinase Kinase and the Ptp2 Protein Tyrosine Phosphatase. Mol Cell Biol. 2008;28: 2481–2494. doi: 10.1128/MCB.01817-07 18212044

55. Hagiwara D, Sakamoto K, Abe K, Gomi K. Signaling pathways for stress responses and adaptation in Aspergillus species: Stress biology in the post-genomic era. Biosc Biotech Biochem. Taylor & Francis; 2016;80: 1667–1680. doi: 10.1080/09168451.2016.1162085 27007956

56. Furukawa K, Hoshi Y, Maeda T, Nakajima T, Abe K. Aspergillus nidulans HOG pathway is activated only by two-component signalling pathway in response to osmotic stress. Mol Microbiol. 2005;56: 1246–1261. doi: 10.1111/j.1365-2958.2005.04605.x 15882418

57. Yu Z, Fischer R. Light sensing and responses in fungi. Nat Rev Microbiol. Springer US; 2019;17: 25–36. doi: 10.1038/s41579-018-0109-x 30377305

58. de Assis LJ, Ries LNA, Savoldi M, Dinamarco TM, Goldman GH, Brown NA. Multiple Phosphatases Regulate Carbon Source-Dependent Germination and Primary Metabolism in Aspergillus nidulans. G3 Genes|Genomes|Genetics. 2015;5: 857–872. doi: 10.1534/g3.115.016667 25762568

59. Son S, Osmani S a. Analysis of all protein phosphatase genes in Aspergillus nidulans identifies a new mitotic regulator, fcp1. Eukaryot Cell. 2009;8: 573–85. doi: 10.1128/EC.00346-08 19181872

60. Taus T, Köcher T, Pichler P, Paschke C, Schmidt A, Henrich C, et al. Universal and confident phosphorylation site localization using phosphoRS. J Proteome Res. 2011;10: 5354–5362. doi: 10.1021/pr200611n 22073976


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