#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Fungal Communication Requires the MAK-2 Pathway Elements STE-20 and RAS-2, the NRC-1 Adapter STE-50 and the MAP Kinase Scaffold HAM-5


Appropriate cellular responses to external stimuli depend on the highly orchestrated activity of interconnected signaling cascades. One crucial level of control arises from the formation of discrete complexes through scaffold proteins that bind multiple components of a given pathway. Central for our understanding of these signaling platforms is the archetypical MAP kinase scaffold Ste5p, a protein that is restricted to budding yeast and close relatives. We identified HAM-5, a protein highly conserved in filamentous ascomycete fungi, as cell–cell communication-specific scaffold protein of the Neurospora crassa MAK-2 cascade (homologous to the budding yeast pheromone pathway). We also describe a network of upstream acting proteins, consisting of two Ste20-related kinases, the small G-protein RAS-2 and the adenylate cyclase capping protein CAP-1, whose signals converge on HAM-5. Our work has implications for the mechanistic understanding of MAP kinase scaffold proteins and their function during intercellular communication in eukaryotic microbes as well as higher eukaryotes.


Vyšlo v časopise: Fungal Communication Requires the MAK-2 Pathway Elements STE-20 and RAS-2, the NRC-1 Adapter STE-50 and the MAP Kinase Scaffold HAM-5. PLoS Genet 10(11): e32767. doi:10.1371/journal.pgen.1004762
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004762

Souhrn

Appropriate cellular responses to external stimuli depend on the highly orchestrated activity of interconnected signaling cascades. One crucial level of control arises from the formation of discrete complexes through scaffold proteins that bind multiple components of a given pathway. Central for our understanding of these signaling platforms is the archetypical MAP kinase scaffold Ste5p, a protein that is restricted to budding yeast and close relatives. We identified HAM-5, a protein highly conserved in filamentous ascomycete fungi, as cell–cell communication-specific scaffold protein of the Neurospora crassa MAK-2 cascade (homologous to the budding yeast pheromone pathway). We also describe a network of upstream acting proteins, consisting of two Ste20-related kinases, the small G-protein RAS-2 and the adenylate cyclase capping protein CAP-1, whose signals converge on HAM-5. Our work has implications for the mechanistic understanding of MAP kinase scaffold proteins and their function during intercellular communication in eukaryotic microbes as well as higher eukaryotes.


Zdroje

1. Van NormanJM, BreakfieldNW, BenfeyPN (2011) Intercellular communication during plant development. Plant Cell 23: 855–864.

2. CelikerH, GoreJ (2013) Cellular cooperation: insights from microbes. Trends Cell Biol 23: 9–15.

3. KornbergTB, RoyS (2014) Communicating by touch - neurons are not alone. Trends Cell Biol 24: 370–376.

4. BloemendalS, KuckU (2013) Cell-to-cell communication in plants, animals, and fungi: a comparative review. Naturwissenschaften 100: 3–19.

5. LeederAC, Palma-GuerreroJ, GlassNL (2011) The social network: deciphering fungal language. Nat Rev Microbiol 9: 440–451.

6. SimoninA, Palma-GuerreroJ, FrickerM, GlassNL (2012) Physiological significance of network organization in fungi. Eukaryot Cell 11: 1345–1352.

7. RichardF, GlassNL, PringleA (2012) Cooperation among germinating spores facilitates the growth of the fungus, Neurospora crassa. Biol Lett 8: 419–422.

8. CravenKD, VelezH, ChoY, LawrenceCB, MitchellTK (2008) Anastomosis is required for virulence of the fungal necrotroph Alternaria brassicicola. Eukaryot Cell 7: 675–683.

9. CharltonND, ShojiJY, GhimireSR, NakashimaJ, CravenKD (2012) Deletion of the fungal gene soft disrupts mutualistic symbiosis between the grass endophyte Epichloe festucae and the host plant. Eukaryot Cell 11: 1463–1471.

10. RocaMG, WeichertM, SiegmundU, TudzynskiP, FleissnerA (2012) Germling fusion via conidial anastomosis tubes in the grey mould Botrytis cinerea requires NADPH oxidase activity. Fungal Biol 116: 379–387.

11. EatonCJ, CoxMP, ScottB (2011) What triggers grass endophytes to switch from mutualism to pathogenism? Plant Sci 180: 190–195.

12. IshikawaFH, SouzaEA, ShojiJY, ConnollyL, FreitagM, et al. (2012) Heterokaryon incompatibility is suppressed following conidial anastomosis tube fusion in a fungal plant pathogen. PLoS One 7: e31175.

13. Oren-SuissaM, PodbilewiczB (2010) Evolution of programmed cell fusion: common mechanisms and distinct functions. Dev Dyn 239: 1515–1528.

14. AguilarPS, BayliesMK, FleissnerA, HelmingL, InoueN, et al. (2013) Genetic basis of cell-cell fusion mechanisms. Trends Genet 29: 427–437.

15. ReadND, LichiusA, ShojiJY, GoryachevAB (2009) Self-signalling and self-fusion in filamentous fungi. Curr Opin Microbiol 12: 608–615.

16. FleissnerA, LeederAC, RocaMG, ReadND, GlassNL (2009) Oscillatory recruitment of signaling proteins to cell tips promotes coordinated behavior during cell fusion. Proc Natl Acad Sci U S A 106: 19387–19392.

17. DettmannA, IllgenJ, MaerzS, SchurgT, FleissnerA, et al. (2012) The NDR kinase scaffold HYM1/MO25 is essential for MAK2 map kinase signaling in Neurospora crassa. PLoS Genet 8: e1002950.

18. GoryachevAB, LichiusA, WrightGD, ReadND (2012) Excitable behavior can explain the “ping-pong” mode of communication between cells using the same chemoattractant. Bioessays 34: 259–266.

19. BorkovichKA, AlexLA, YardenO, FreitagM, TurnerGE, et al. (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.

20. RispailN, SoanesDM, AntC, CzajkowskiR, GrunlerA, et al. (2009) Comparative genomics of MAP kinase and calcium-calcineurin signalling components in plant and human pathogenic fungi. Fungal Genet Biol 46: 287–298.

21. QiM, ElionEA (2005) MAP kinase pathways. J Cell Sci 118: 3569–3572.

22. GalaganJE, CalvoSE, BorkovichKA, SelkerEU, ReadND, et al. (2003) The genome sequence of the filamentous fungus Neurospora crassa. Nature 422: 859–868.

23. ReadND, GoryachevAB, LichiusA (2012) The mechanistic basis of self-fusion between conidial anastomosis tubes during fungal colony initiation. Fungal Biology Reviews 26: 1–11.

24. XiangQ, RasmussenC, GlassNL (2002) The ham-2 locus, encoding a putative transmembrane protein, is required for hyphal fusion in Neurospora crassa. Genetics 160: 169–180.

25. MaerzS, DettmannA, ZivC, LiuY, ValeriusO, et al. (2009) Two NDR kinase-MOB complexes function as distinct modules during septum formation and tip extension in Neurospora crassa. Mol Microbiol 74: 707–723.

26. SimoninAR, RasmussenCG, YangM, GlassNL (2010) Genes encoding a striatin-like protein (ham-3) and a forkhead associated protein (ham-4) are required for hyphal fusion in Neurospora crassa. Fungal Genet Biol 47: 855–868.

27. BloemendalS, BernhardsY, BarthoK, DettmannA, VoigtO, et al. (2012) A homologue of the human STRIPAK complex controls sexual development in fungi. Mol Microbiol 84: 310–323.

28. DettmannA, HeiligY, LudwigS, SchmittK, IllgenJ, et al. (2013) HAM-2 and HAM-3 are central for the assembly of the Neurospora STRIPAK complex at the nuclear envelope and regulate nuclear accumulation of the MAP kinase MAK-1 in a MAK-2-dependent manner. Mol Microbiol 90: 796–812.

29. FuC, IyerP, HerkalA, AbdullahJ, StoutA, et al. (2011) Identification and characterization of genes required for cell-to-cell fusion in Neurospora crassa. Eukaryot Cell 10: 1100–1109.

30. AldabbousMS, RocaMG, StoutA, HuangIC, ReadND, et al. (2010) The ham-5, rcm-1 and rco-1 genes regulate hyphal fusion in Neurospora crassa. Microbiology 156: 2621–2629.

31. LiD, BobrowiczP, WilkinsonHH, EbboleDJ (2005) A mitogen-activated protein kinase pathway essential for mating and contributing to vegetative growth in Neurospora crassa. Genetics 170: 1091–1104.

32. LeederAC, JonkersW, LiJ, GlassNL (2013) Early colony establishment in Neurospora crassa requires a MAP kinase regulatory network. Genetics 195: 883–898.

33. ChenRE, ThornerJ (2007) Function and regulation in MAPK signaling pathways: lessons learned from the yeast Saccharomyces cerevisiae. Biochim Biophys Acta 1773: 1311–1340.

34. SaitoH (2010) Regulation of cross-talk in yeast MAPK signaling pathways. Curr Opin Microbiol 13: 677–683.

35. QiaoF, BowieJU (2005) The many faces of SAM. Sci STKE 2005: re7.

36. GrimshawSJ, MottHR, StottKM, NielsenPR, EvettsKA, et al. (2004) Structure of the sterile alpha motif (SAM) domain of the Saccharomyces cerevisiae mitogen-activated protein kinase pathway-modulating protein STE50 and analysis of its interaction with the STE11 SAM. J Biol Chem 279: 2192–2201.

37. TrucksesDM, BloomekatzJE, ThornerJ (2006) The RA domain of Ste50 adaptor protein is required for delivery of Ste11 to the plasma membrane in the filamentous growth signaling pathway of the yeast Saccharomyces cerevisiae. Mol Cell Biol 26: 912–928.

38. WuC, JansenG, ZhangJ, ThomasDY, WhitewayM (2006) Adaptor protein Ste50p links the Ste11p MEKK to the HOG pathway through plasma membrane association. Genes Dev 20: 734–746.

39. SchamberA, LerochM, DiwoJ, MendgenK, HahnM (2010) The role of mitogen-activated protein (MAP) kinase signalling components and the Ste12 transcription factor in germination and pathogenicity of Botrytis cinerea. Mol Plant Pathol 11: 105–119.

40. ParkG, XueC, ZhaoX, KimY, OrbachM, et al. (2006) Multiple upstream signals converge on the adaptor protein Mst50 in Magnaporthe grisea. Plant Cell 18: 2822–2835.

41. FuJ, MaresC, LizcanoA, LiuY, WickesBL (2011) Insertional mutagenesis combined with an inducible filamentation phenotype reveals a conserved STE50 homologue in Cryptococcus neoformans that is required for monokaryotic fruiting and sexual reproduction. Mol Microbiol 79: 990–1007.

42. BayramO, BayramOS, AhmedYL, MaruyamaJ, ValeriusO, et al. (2012) The Aspergillus nidulans MAPK module AnSte11-Ste50-Ste7-Fus3 controls development and secondary metabolism. PLoS Genet 8: e1002816.

43. PandeyA, RocaMG, ReadND, GlassNL (2004) Role of a mitogen-activated protein kinase pathway during conidial germination and hyphal fusion in Neurospora crassa. Eukaryot Cell 3: 348–358.

44. MaerzS, ZivC, VogtN, HelmstaedtK, CohenN, et al. (2008) The nuclear Dbf2-related kinase COT1 and the mitogen-activated protein kinases MAK1 and MAK2 genetically interact to regulate filamentous growth, hyphal fusion and sexual development in Neurospora crassa. Genetics 179: 1313–1325.

45. Jamet-ViernyC, DebuchyR, PrigentM, SilarP (2007) IDC1, a pezizomycotina-specific gene that belongs to the PaMpk1 MAP kinase transduction cascade of the filamentous fungus Podospora anserina. Fungal Genet Biol 44: 1219–1230.

46. BeldenWJ, LarrondoLF, FroehlichAC, ShiM, ChenCH, et al. (2007) The band mutation in Neurospora crassa is a dominant allele of ras-1 implicating RAS signaling in circadian output. Genes Dev 21: 1494–1505.

47. HeiligY, DettmannA, Mourino-PerezRR, SchmittK, ValeriusO, et al. (2014) Proper actin ring formation and septum constriction requires coordinated regulation of SIN and MOR pathways through the germinal centre kinase MST-1. PLoS Genet 10: e1004306.

48. HeiligY, SchmittK, StephanSeiler (2013) S (2013) Phospho-regulation of the Neurospora crassa septation initiation network. PLOS One 8: e79464.

49. Kana-uchiA, YamashiroCT, TanabeS, MurayamaT (1997) A ras homologue of Neurospora crassa regulates morphology. Mol Gen Genet 254: 427–432.

50. RocaMG, ArltJ, JeffreeCE, ReadND (2005) Cell biology of conidial anastomosis tubes in Neurospora crassa. Eukaryot Cell 4: 911–919.

51. KramerB, ThinesE, FosterAJ (2009) MAP kinase signalling pathway components and targets conserved between the distantly related plant pathogenic fungi Mycosphaerella graminicola and Magnaporthe grisea. Fungal Genet Biol 46: 667–681.

52. DardN, PeterM (2006) Scaffold proteins in MAP kinase signaling: more than simple passive activating platforms. Bioessays 28: 146–156.

53. WitzelF, MaddisonL, BluthgenN (2012) How scaffolds shape MAPK signaling: what we know and opportunities for systems approaches. Front Physiol 3: 475.

54. CoteP, SuleaT, DignardD, WuC, WhitewayM (2011) Evolutionary reshaping of fungal mating pathway scaffold proteins. MBio 2: e00230–00210.

55. JonkersW, LeederAC, AnsongC, YangF, Camp IIDG, et al. (2014) HAM-5 functions as a MAP kinase scaffold during cell fusion in Neurospora crassa. PLoS Genet 10: e1004783.

56. FilippiBM, de los HerosP, MehellouY, NavratilovaI, GourlayR, et al. (2011) MO25 is a master regulator of SPAK/OSR1 and MST3/MST4/YSK1 protein kinases. EMBO J 30: 1730–1741.

57. GourlayCW, AyscoughKR (2006) Actin-induced hyperactivation of the Ras signaling pathway leads to apoptosis in Saccharomyces cerevisiae. Mol Cell Biol 26: 6487–6501.

58. FieldJ, VojtekA, BallesterR, BolgerG, ColicelliJ, et al. (1990) Cloning and characterization of CAP, the S. cerevisiae gene encoding the 70 kd adenylyl cyclase-associated protein. Cell 61: 319–327.

59. ZhouX, ZhangH, LiG, ShawB, XuJR (2012) The Cyclase-associated protein Cap1 is important for proper regulation of infection-related morphogenesis in Magnaporthe oryzae. PLoS Pathog 8: e1002911.

60. RochaCR, SchroppelK, HarcusD, MarcilA, DignardD, et al. (2001) Signaling through adenylyl cyclase is essential for hyphal growth and virulence in the pathogenic fungus Candida albicans. Mol Biol Cell 12: 3631–3643.

61. BertlingE, Quintero-MonzonO, MattilaPK, GoodeBL, LappalainenP (2007) Mechanism and biological role of profilin-Srv2/CAP interaction. J Cell Sci 120: 1225–1234.

62. MoriyamaK, YaharaI (2002) Human CAP1 is a key factor in the recycling of cofilin and actin for rapid actin turnover. J Cell Sci 115: 1591–1601.

63. LichiusA, GoryachevAB, FrickerMD, ObaraB, Castro-LongoriaE, et al. (2014) CDC-42 and RAC-1 regulate opposite chemotropisms in Neurospora crassa. J Cell Sci 127: 1953–1965.

64. FrieserSH, HlubekA, SandrockB, BolkerM (2011) Cla4 kinase triggers destruction of the Rac1-GEF Cdc24 during polarized growth in Ustilago maydis. Mol Biol Cell 22: 3253–3262.

65. SchuergT, BrandtU, AdisC, FleissnerA (2012) The Saccharomyces cerevisiae BEM1 homologue in Neurospora crassa promotes co-ordinated cell behaviour resulting in cell fusion. Mol Microbiol 86: 349–366.

66. Araujo-PalomaresCL, RichthammerC, SeilerS, Castro-LongoriaE (2011) Functional characterization and cellular dynamics of the CDC-42 - RAC - CDC-24 module in Neurospora crassa. PLoS One 6: e27148.

67. RiquelmeM, YardenO, Bartnicki-GarciaS, BowmanB, Castro-LongoriaE, et al. (2011) Architecture and development of the Neurospora crassa hypha — a model cell for polarized growth. Fungal Biol 115: 446–474.

68. SeilerS, Justa-SchuchD (2010) Conserved components, but distinct mechanisms for the placement and assembly of the cell division machinery in unicellular and filamentous ascomycetes. Mol Microbiol 78: 1058–1076.

69. JeddG, PieuchotL (2012) Multiple modes for gatekeeping at fungal cell-to-cell channels. Mol Microbiol 86: 1291–1294.

70. HericheJK, LebrinF, RabilloudT, LeroyD, ChambazEM, et al. (1997) Regulation of protein phosphatase 2A by direct interaction with casein kinase 2alpha. Science 276: 952–955.

71. LebrinF, BianchiniL, RabilloudT, ChambazEM, GoldbergY (1999) CK2alpha-protein phosphatase 2A molecular complex: possible interaction with the MAP kinase pathway. Mol Cell Biochem 191: 207–212.

72. GoudreaultM, D'AmbrosioLM, KeanMJ, MullinMJ, LarsenBG, et al. (2009) A PP2A phosphatase high density interaction network identifies a novel striatin-interacting phosphatase and kinase complex linked to the cerebral cavernous malformation 3 (CCM3) protein. Mol Cell Proteomics 8: 157–171.

73. GarrentonLS, StefanCJ, McMurrayMA, EmrSD, ThornerJ (2010) Pheromone-induced anisotropy in yeast plasma membrane phosphatidylinositol-4,5-bisphosphate distribution is required for MAPK signaling. Proc Natl Acad Sci U S A 107: 11805–11810.

74. MahsA, IschebeckT, HeiligY, StenzelI, HempelF, et al. (2012) The essential phosphoinositide kinase MSS-4 is required for polar hyphal morphogenesis, localizing to sites of growth and cell fusion in Neurospora crassa. PLoS One 7: e51454.

75. RoelantsFM, BaltzAG, TrottAE, FereresS, ThornerJ (2010) A protein kinase network regulates the function of aminophospholipid flippases. Proc Natl Acad Sci U S A 107: 34–39.

76. NakanoK, YamamotoT, KishimotoT, NojiT, TanakaK (2008) Protein kinases Fpk1p and Fpk2p are novel regulators of phospholipid asymmetry. Mol Biol Cell 19: 1783–1797.

77. SaitoK, Fujimura-KamadaK, HanamatsuH, KatoU, UmedaM, et al. (2007) Transbilayer phospholipid flipping regulates Cdc42p signaling during polarized cell growth via Rga GTPase-activating proteins. Dev Cell 13: 743–751.

78. KotheGO, FreeSJ (1998) The isolation and characterization of nrc-1 and nrc-2, two genes encoding protein kinases that control growth and development in Neurospora crassa. Genetics 149: 117–130.

79. SeilerS, PlamannM (2003) The genetic basis of cellular morphogenesis in the filamentous fungus Neurospora crassa. Mol Biol Cell 14: 4352–4364.

80. FreitagM, HickeyPC, RajuNB, SelkerEU, ReadND (2004) GFP as a tool to analyze the organization, dynamics and function of nuclei and microtubules in Neurospora crassa. Fungal Genet Biol 41: 897–910.

81. HondaS, SelkerEU (2009) Tools for fungal proteomics: multifunctional neurospora vectors for gene replacement, protein expression and protein purification. Genetics 182: 11–23.

82. VerdinJ, Bartnicki-GarciaS, RiquelmeM (2009) Functional stratification of the Spitzenkorper of Neurospora crassa. Mol Microbiol 74: 1044–1053.

83. MaerzS, DettmannA, SeilerS (2012) Hydrophobic Motif Phosphorylation Coordinates Activity and Polar Localization of the Neurospora crassa Nuclear Dbf2-Related Kinase COT1. Mol Cell Biol 32: 2083–2098.

84. SeilerS, VogtN, ZivC, GorovitsR, YardenO (2006) The STE20/germinal center kinase POD6 interacts with the NDR kinase COT1 and is involved in polar tip extension in Neurospora crassa. Mol Biol Cell 17: 4080–4092.

85. RichthammerC, EnseleitM, Sanchez-LeonE, MarzS, HeiligY, et al. (2012) RHO1 and RHO2 share partially overlapping functions in the regulation of cell wall integrity and hyphal polarity in Neurospora crassa. Mol Microbiol 85: 716–733.

86. MaddiA, DettmanA, FuC, SeilerS, FreeSJ (2012) WSC-1 and HAM-7 are MAK-1 MAP kinase pathway sensors required for cell wall integrity and hyphal fusion in Neurospora crassa. PLoS One 7: e42374.

87. FuC, AoJ, DettmannA, SeilerS, FreeSJ (2014) Characterization of the Neurospora crassa cell fusion proteins HAM-6, HAM-7, HAM-8, HAM-9, HAM-10, AMPH-1 and WHI-2. PLoS ONE 9: e107773.

88. RiquelmeM, BredewegEL, Callejas-NegreteO, RobersonRW, LudwigS, et al. (2014) The Neurospora crassa exocyst complex tethers Spitzenkorper vesicles to the apical plasma membrane during polarized growth. Mol Biol Cell 25: 1312–1326.

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2014 Číslo 11
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Získaná hemofilie - Povědomí o nemoci a její diagnostika
nový kurz

Eozinofilní granulomatóza s polyangiitidou
Autori: doc. MUDr. Martina Doubková, Ph.D.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#