Large-Scale Analysis of Kinase Signaling in Yeast Pseudohyphal Development Identifies Regulation of Ribonucleoprotein Granules

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Eukaryotic cells affect precise changes in shape and growth in response to environmental and nutritional stress, enabling cell survival and wild-type function. The single-celled budding yeast provides a striking example, undergoing a set of changes under conditions of nitrogen or glucose limitation resulting in the formation of extended cellular chains or filaments. Related filamentous growth transitions are required for virulence in pathogenic fungi and have been studied extensively; however, the full scope of signaling underlying the filamentous growth transition remains to be determined. Here, we used a combination of genetics and proteomics to identify proteins that undergo phosphorylation dependent upon kinases required for filamentous growth. Within this protein set, we identified novel sites of phosphorylation in the yeast proteome and extensive phosphorylation of mRNA-protein complexes regulating mRNA decay and translation. The data indicate an interrelationship between filamentous growth and these ubiquitously conserved sites of RNA regulation: the RNA-protein complexes are required for the filamentous growth transition, and a well studied filamentous growth signaling kinase is required for wild-type numbers of RNA-protein complexes. This interdependence is previously unappreciated, highlighting an additional level of translational control underlying this complex growth transition.

Vyšlo v časopise: Large-Scale Analysis of Kinase Signaling in Yeast Pseudohyphal Development Identifies Regulation of Ribonucleoprotein Granules. PLoS Genet 11(10): e32767. doi:10.1371/journal.pgen.1005564
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005564

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Zdroje

1. Gimeno CJ, Ljungdahl PO, Styles CA, Fink GR. Unipolar cell divisions in the yeast S. cerevisiae lead to filamentous growth: regulation by starvation and RAS. Cell. 1992; 68:1077–90. 1547504.

2. Lo WS, Dranginis AM. FLO11, a yeast gene related to the STA genes, encodes a novel cell surface flocculin. J Bacteriol. 1996; 178:7144–51. 8955395

3. Erdman S, Snyder M. A filamentous growth response mediated by the yeast mating pathway. Genetics. 2001; 159:919–28. PMCID: PMC1461863.

4. Grenson M. Multiplicity of the amino acid permeases in Saccharomyces cerevisiae: Evidence for a specific lysine-transporting system. Biochim Biophys Acta. 1996; 127:339–46. 5964978.

5. Song Q, Johnson C, Wilson TE, Kumar A. Pooled segregant sequencing reveals genetic determinants of yeast pseudohyphal growth. PLoS Genet. 2014; 10:e1004570. PMCID: PMC4140661. doi: 10.1371/journal.pgen.1004570

6. Dickinson JR. Fusel alcohols induce hyphal-like extensions and pseudohyphal formation in yeasts. Microbiology. 1996; 142:1391–7. 8704979.

7. Lambrechts MG, Bauer FF, Marmur J, Pretorius IS. Muc1, a mucin-like protein that is regulated by Mss10, is critical for pseudohyphal differentiation in yeast. Proc Natl Acad Sci U S A. 1996; 93:8419–24. 8710886

8. Cullen PJ, Sprague GF. Glucose depletion causes haploid invasive growth in yeast. Proc Natl Acad Sci U S A. 2000; 97:13461–3. 11095711

9. Lorenz MC, Cutler NS, Heitman J. Characterization of alcohol-induced filamentous growth in Saccharomyces cerevisiae. Mol Biol Cell. 2000; 11:183–99. 10637301.

10. Gancedo JM. Control of pseudohyphae formation in Saccharomyces cerevisiae. FEMS Microbiol Rev. 2001; 25:107–23. 11152942.

11. Odds FC. Morphogenesis in Candida albicans. Crit Rev Microbiol. 1985; 12:45–93. 3893894.

12. Mitchell AP. Dimorphism and virulence in Candida albicans. Current Opin Microbiol. 1998; 1:687–92. 10066539.

13. Sudbery P, Gow N, Berman J. The distinct morphogenic states of Candida albicans. Trends Microbiol. 2004; 12:317–24. 15223059.

14. Lo HJ, Kohler J, DiDomenico B, Loebenberg D, Cacciapuoti A, Fink GR. Nonfilamentous C. albicans mutants are avirulent. Cell. 1997; 90:939–49. 9298905

15. Braun BR, Johnson AD. Control of filament formation in Candida albicans by the transcriptional repressor TUP1. Science. 1997; 277:105–9. 9204892.

16. Saville SP, Lazzell AL, Monteagudo C, Lopez-Ribot JL. Engineered control of cell morphology in vivo reveals distinct roles for yeast and filamentous forms of Candida albicans during infection. Eukaryot Cell. 2003; 2:1053–60. 14555488.

17. Ahn SH, Acurio A, Kron SJ. Regulation of G2/M progression by the STE mitogen-activated protein kinase pathway in budding yeast filamentous growth. Mol Biol Cell. 1999; 10:3301–16. 10512868.

18. Miled C, Mann C, Faye G. Xbp1-mediated repression of CLB gene expression contributes to the modifications of yeast cell morphology and cell cycle seen during nitrogen-limited growth. Mol Cell Biol. 2001; 21:3714–24. 11340165.

19. Cullen PJ, Sabbagh W, Graham E, Irick MM, van Olden EK, Neal C, et al. A signaling mucin at the head of the Cdc42- and MAPK-dependent filamentous growth pathway in yeast. Genes Dev. 2004;18:1695–708. 15256499

20. Karunanithi S, Vadaie N, Chavel CA, Birkaya B, Joshi J, Grell L, et al. Shedding of the mucin-like flocculin Flo11p reveals a new aspect of fungal adhesion regulation. Curr Biol. 2010; 20:1389–95. 20619652. doi: 10.1016/j.cub.2010.06.033

21. Liu H, Styles CA, Fink GR. Elements of the yeast pheromone response pathway required for filamentous growth of diploids. Science. 1993; 262:1741–4. 8259520

22. Madhani HD, Styles CA, Fink GR. MAP kinases with distinct inhibitory functions impart signaling specificity during yeast differentiation. Cell. 1997; 91:673–84. 9393860.

23. Buehrer BM, Errede B. Coordination of the mating and cell integrity mitogen-activated protein kinase pathways in Saccharomyces cerevisiae. Mol Cell Biol. 1997; 17:6517–25. 9343415

24. Cook JG, Bardwell L, Kron SJ, Thorner J. Two novel targets of the MAP kinase Kss1 are negative regulators of invasive growth in the yeast Saccharomyces cerevisiae. Genes Dev. 1996; 10:2831–48. 8918885.

25. Bardwell L, Cook JG, Voora D, Baggott DM, Martinez AR, Thorner J. Repression of yeast Ste12 transcription factor by direct binding of unphosphorylated Kss1 MAPK and its regulation by the Ste7 MEK. Genes Dev. 1998; 12:2887–98. 9744865

26. Elion EA, Brill JA, Fink GR. FUS3 represses CLN1 and CLN2 and in concert with KSS1 promotes signal transduction. Proc Natl Acad Sci U S A. 1991; 88:9392–6. 1946350.

27. Madhani HD, Fink GR. Combinatorial control required for the specificity of yeast MAPK signaling. Science. 1997; 275:1314–7. 9036858.

28. Bao MZ, Schwartz MA, Cantin GT, Yates JR, Madhani H. Pheromone-Dependent Destruction of the Tec1 Transcription Factor is Required for MAP Kinase Signaling Specificity in Yeast. Cell. 2004; 119:991–1000. 15620357

29. Toda T, Cameron S, Sass P, Zoller M, Wigler M. Three different genes in S. cerevisiae encode the catalytic subunits of the cAMP-dependent protein kinase. Cell. 1987; 50:277–87. 3036373.

30. Toda T, Cameron S, Sass P, Zoller M, Scott JD, McMullen B, et al. Cloning and characterization of BCY1, a locus encoding a regulatory subunit of the cyclic AMP-dependent protein kinase in Saccharomyces cerevisiae. Mol Cell Biol. 1987; 7:1371–7. 3037314.

31. Robertson LS, Fink GR. The three yeast A kinases have specific signaling functions in pseudohyphal growth. Proc Natl Acad Sci U S A. 1998; 95:13783–7. 9811878.

32. Pan X, Heitman J. Cyclic AMP-dependent protein kinase regulates pseudohyphal differentiation in Saccharomyces cerevisiae. Mol Cell Biol. 1999; 19:4874–87. 10373537.

33. Vyas VK, Kuchin S, Berkey CD, Carlson M. Snf1 kinases with different beta-subunit isoforms play distinct roles in regulating haploid invasive growth. Mol Cell Biol. 2003; 23:1341–8. 12556493.

34. Kuchin S, Vyas VK, Carlson M. Snf1 protein kinase and the repressors Nrg1 and Nrg2 regulate FLO11, haploid invasive growth, and diploid pseudohyphal differentiation. Mol Cell Biol. 2002; 22:3994–4000. 12024013.

35. Rupp S, Summers E, Lo HJ, Madhani H, Fink G. MAP kinase and cAMP filamentation signaling pathways converge on the unusually large promoter of the yeast FLO11 gene. EMBO J. 1999; 18:1257–69. 10064592.

36. van Dyk D, Pretorius IS, Bauer FF. Mss11p is a central element of the regulatory network that controls FLO11 expression and invasive growth in Saccharomyces cerevisiae. Genetics. 2005;169: 91–106. 15466424

37. Sutherland CM, Hawley SA, McCartney RR, Leech A, Stark MJ, Schmidt MC, et al. Elm1p is one of three upstream kinases for the Saccharomyces cerevisiae SNF1 complex. Curr Biol. 2003; 13:1299–305. 12906789.

38. Jin R, Dobry CJ, McCown PJ, Kumar A. Large-scale analysis of yeast filamentous growth by systematic gene disruption and overexpression. Mol Biol Cell. 2008; 19:284–96. 17989363.

39. Ryan O, Shapiro RS, Kurat CF, Mayhew D, Baryshnikova A, Chin B, et al. Global gene deletion analysis exploring yeast filamentous growth. Science. 2012; 337:1353–6. 22984072. doi: 10.1126/science.1224339

40. Shively CA, Eckwahl MJ, Dobry CJ, Mellacheruvu D, Nesvizhskii A, Kumar A. Genetic networks inducing invasive growth in Saccharomyces cerevisiae identified through systematic genome-wide overexpression. Genetics. 2013; 193:1297–310. 23410832. doi: 10.1534/genetics.112.147876

41. Ma J, Jin R, Jia X, Dobry CJ, Wang L, Reggiori F, et al. An interrelationship between autophagy and filamentous growth in budding yeast. Genetics. 2007; 177:205–14. 17890363.

42. Johnson C, Kweon HK, Sheidy D, Shively CA, Mellacheruvu D, Nesvizhskii AI, et al. The yeast sks1p kinase signaling network regulates pseudohyphal growth and glucose response. PLoS Genet. 2014; 10:e1004183. 24603354. doi: 10.1371/journal.pgen.1004183

43. Madhani HD, Galitski T, Lander ES, Fink GR. Effectors of a developmental mitogen-activated protein kinase cascade revealed by expression signatures of signaling mutants. Proc Natl Acad Sci U S A. 1999; 96:12530–5. 10535956.

44. Borneman AR, Leigh-Bell JA, Yu H, Bertone P, Gerstein M, Snyder M. Target hub proteins serve as master regulators of development in yeast. Genes Dev. 2006; 20:435–48. 16449570

45. Gruhler A, Olsen JV, Mohammed S, Mortensen P, Faergeman NJ, Mann M, et al. Quantitative phosphoproteomics applied to the yeast pheromone signaling pathway. Mol Cell Proteomics. 2005; 4:310–27. 15665377

46. Bodenmiller B, Wanka S, Kraft C, Urban J, Campbell D, Pedrioli PG, et al. Phosphoproteomic analysis reveals interconnected system-wide responses to perturbations of kinases and phosphatases in yeast. Sci Signal. 2010; 3:rs4. 21177495. doi: 10.1126/scisignal.2001182

47. Oliveira AP, Ludwig C, Zampieri M, Weisser H, Aebersold R, Sauer U. Dynamic phosphoproteomics reveals TORC1-dependent regulation of yeast nucleotide and amino acid biosynthesis. Sci Signal. 2015; 8:rs4. 25921291. doi: 10.1126/scisignal.2005768

48. Braun KA, Vaga S, Dombek KM, Fang F, Palmisano S, Aebersold R, et al. Phosphoproteomic analysis identifies proteins involved in transcription-coupled mRNA decay as targets of Snf1 signaling. Sci Signal. 2014; 7:ra64. 25005228. doi: 10.1126/scisignal.2005000

49. Ong SE, Blagoev B, Kratchmarova I, Kristensen DB, Steen H, Pandey A, et al. Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics. Mol Cell Proteomics. 2002; 1:376–86. 12118079

50. Mosch HU, Roberts RL, Fink GR. Ras2 signals via the Cdc42/Ste20/mitogen-activated protein kinase module to induce filamentous growth in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1996;93(11):5352–6. 8643578.

51. Kobayashi O, Suda H, Ohtani T, Sone H. Molecular cloning and analysis of the dominant flocculation gene FLO8 from Saccharomyces cerevisiae. Mol Gen Genet. 1996; 251:707–15. 8757402

52. Buchan JR, Parker R. Eukaryotic stress granules: the ins and outs of translation. Mol Cell. 2009; 36:932–41. 20064460. doi: 10.1016/j.molcel.2009.11.020

53. Teixeira D, Sheth U, Valencia-Sanchez MA, Brengues M, Parker R. Processing bodies require RNA for assembly and contain nontranslating mRNAs. RNA. 2005; 11:371–82. 15703442.

54. Kedersha N, Stoecklin G, Ayodele M, Yacono P, Lykke-Andersen J, Fritzler MJ, et al. Stress granules and processing bodies are dynamically linked sites of mRNP remodeling. J Cell Biol. 2005; 169:871–84. 15967811.

55. Buchan JR, Yoon JH, Parker R. Stress-specific composition, assembly and kinetics of stress granules in Saccharomyces cerevisiae. J Cell Sci. 2011; 124:228–39. 21172806. doi: 10.1242/jcs.078444

56. Mitchell SF, Jain S, She M, Parker R. Global analysis of yeast mRNPs. Nat Struct Mol Biol. 2013; 20:127–33. 23222640. doi: 10.1038/nsmb.2468

57. Buchan JR, Nissan T, Parker R. Analyzing P-bodies and stress granules in Saccharomyces cerevisiae. Methods Enzymol. 2010; 470:619–40. 20946828. doi: 10.1016/S0076-6879(10)70025-2

58. Talarek N, Cameroni E, Jaquenoud M, Luo X, Bontron S, Lippman S, et al. Initiation of the TORC1-regulated G0 program requires Igo1/2, which license specific mRNAs to evade degradation via the 5'-3' mRNA decay pathway. Mol Cell. 2010; 38:345–55. 20471941. doi: 10.1016/j.molcel.2010.02.039

59. Brodsky AS, Silver PA. Pre-mRNA processing factors are required for nuclear export. RNA. 2000; 6:1737–49. 11142374.

60. Sheth U, Parker R. Decapping and decay of messenger RNA occur in cytoplasmic processing bodies. Science. 2003; 300:805–8. 12730603.

61. Granek JA, Magwene PM. Environmental and genetic determinants of colony morphology in yeast. PLoS Genet. 2010; 6:e1000823. 20107600. doi: 10.1371/journal.pgen.1000823

62. Bouveret E, Rigaut G, Shevchenko A, Wilm M, Seraphin B. A Sm-like protein complex that participates in mRNA degradation. EMBO J. 2000; 19:1661–71. 10747033.

63. Maleri S, Ge Q, Hackett EA, Wang Y, Dohlman HG, Errede B. Persistent activation by constitutive Ste7 promotes Kss1-mediated invasive growth but fails to support Fus3-dependent mating in yeast. Mol Cell Biol. 2004; 24:9221–38. 15456892.

64. Ptacek J, Devgan G, Michaud G, Zhu H, Zhu X, Fasolo J, et al. Global analysis of protein phosphorylation in yeast. Nature. 2005; 438:679–84. 16319894.

65. Yoon JH, Choi EJ, Parker R. Dcp2 phosphorylation by Ste20 modulates stress granule assembly and mRNA decay in Saccharomyces cerevisiae. J Cell Biol. 2010; 189:813–27. 20513766. doi: 10.1083/jcb.200912019

66. Shah KH, Zhang B, Ramachandran V, Herman PK. Processing body and stress granule assembly occur by independent and differentially regulated pathways in Saccharomyces cerevisiae. Genetics. 2013; 193:109–23. 23105015. doi: 10.1534/genetics.112.146993

67. Shah KH, Nostramo R, Zhang B, Varia SN, Klett BM, Herman PK. Protein kinases are associated with multiple, distinct cytoplasmic granules in quiescent yeast cells. Genetics. 2014; 198:1495–512. 25342717. doi: 10.1534/genetics.114.172031

68. Buchan JR, Muhlrad D, Parker R. P bodies promote stress granule assembly in Saccharomyces cerevisiae. J Cell Biol. 2008; 183:441–55. 18981231. doi: 10.1083/jcb.200807043

69. Choi KY, Kranz JE, Mahanty SK, Park KS, Elion EA. Characterization of Fus3 localization: active Fus3 localizes in complexes of varying size and specific activity. Mol Biol Cell. 1999; 10:1553–68. 10233162.

70. Ma D, Cook JG, Thorner J. Phosphorylation and localization of Kss1, a MAP kinase of the Saccharomyces cerevisiae pheromone response pathway. Mol Biol Cell. 1995; 6:889–909. 7579701.

71. Zhu H, Klemic JF, Chang S, Bertone P, Casamayor A, Klemic KG, et al. Nat Genet. 2000; 26:283–9. 11062466.

72. Jona G, Choder M, Gileadi O. Glucose starvation induces a drastic reduction in the rates of both transcription and degradation of mRNA in yeast. Biochim Biophys Acta. 2000; 1491:37–48. 10760568.

73. Benard L. Inhibition of 5' to 3' mRNA degradation under stress conditions in Saccharomyces cerevisiae: from GCN4 to MET16. RNA. 2004; 10:458–68. 14970391.

74. Hilgers V, Teixeira D, Parker R. Translation-independent inhibition of mRNA deadenylation during stress in Saccharomyces cerevisiae. RNA. 2006; 12:1835–45. 16940550.

75. Berman J, Sudbery PE. Candida Albicans: a molecular revolution built on lessons from budding yeast. Nature Rev Genet. 2002; 3:918–30. 12459722.

76. Jung JH, Kim J. Accumulation of P-bodies in Candida albicans under different stress and filamentous growth conditions. Fungal Genet Biol. 2011; 48:1116–23. 22056521. doi: 10.1016/j.fgb.2011.10.003

77. Bharucha N, Ma J, Dobry CJ, Lawson SK, Yang Z, Kumar A. Analysis of the Yeast Kinome Reveals a Network of Regulated Protein Localization During Filamentous Growth. Mol Biol Cell. 2008; 19:2708–17. 18417610. doi: 10.1091/mbc.E07-11-1199

78. Xu T, Shively CA, Jin R, Eckwahl MJ, Dobry CJ, Song Q, et al. A profile of differentially abundant proteins at the yeast cell periphery during pseudohyphal growth. J Biol Chem. 2010; 285:15476–88. 20228058. doi: 10.1074/jbc.M110.114926

79. Kumar A, DesEtages S, Coelho P, Roeder G, Snyder M. High-throughput methods for the large-scale analysis of gene function by transposon tagging. Methods Enzymol. 2000; 328:550–74. 11075366

80. Ma J, Dobry CJ, Krysan DJ, Kumar A. Unconventional genomic architecture in the budding yeast saccharomyces cerevisiae masks the nested antisense gene NAG1. Eukaryot Cell. 2008; 7:1289–98. 18310357. doi: 10.1128/EC.00053-08

81. Xu T, Johnson CA, Gestwicki JE, Kumar A. Conditionally controlling nuclear trafficking in yeast by chemical-induced protein dimerization. Nat Protoc. 2010; 5:1831–43. 21030958. doi: 10.1038/nprot.2010.141

82. Longtine MS, McKenzie A III, Demarini DJ, Shah NG, Wach A, Brachat A, et al. Additional Modules for Versatile and Economical PCR-based Gene Deletion and Modification in Saccharomyces cerevisiae. Yeast. 1998; 14:953–61. 9717241

83. Zhang Y, Kweon HK, Shively CA, Kumar A, Andrews PC. Towards Systematic Discovery of Signaling Networks in Budding Yeast Filamentous Growth Stress Response Using Interventional Phosphorylation Data. PLoS Comput Biol. 2013; 9:e1003077. doi: 10.1371/journal.pcbi.1003077 23825934

84. Cox J, Matic I, Hilger M, Nagaraj N, Selbach M, Olsen JV, et al. A practical guide to the MaxQuant computational platform for SILAC-based quantitative proteomics. Nat Protoc. 2009; 4:698–705. 19373234. doi: 10.1038/nprot.2009.36

85. Wiwatwattana N, Landau CM, Cope GJ, Harp GA, Kumar A. Organelle DB: an updated resource of eukayotic protein localization and function. Nucleic Acids Res. 2007; 35:D810–D4. 17130152

86. Bharucha N, Chabrier-Rosello Y, Xu T, Johnson C, Sobczynski S, Song Q, et al. A Large-Scale Complex Haploinsufficiency-Based Genetic Interaction Screen in Candida albicans: Analysis of the RAM Network during Morphogenesis. PLoS Genet. 2011; 7:e1002058. 21559071. doi: 10.1371/journal.pgen.1002058