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Network Modeling Reveals Prevalent Negative Regulatory Relationships between Signaling Sectors in Arabidopsis Immune Signaling


Biological signaling processes may be mediated by complex networks in which network components and network sectors interact with each other in complex ways. Studies of complex networks benefit from approaches in which the roles of individual components are considered in the context of the network. The plant immune signaling network, which controls inducible responses to pathogen attack, is such a complex network. We studied the Arabidopsis immune signaling network upon challenge with a strain of the bacterial pathogen Pseudomonas syringae expressing the effector protein AvrRpt2 (Pto DC3000 AvrRpt2). This bacterial strain feeds multiple inputs into the signaling network, allowing many parts of the network to be activated at once. mRNA profiles for 571 immune response genes of 22 Arabidopsis immunity mutants and wild type were collected 6 hours after inoculation with Pto DC3000 AvrRpt2. The mRNA profiles were analyzed as detailed descriptions of changes in the network state resulting from the genetic perturbations. Regulatory relationships among the genes corresponding to the mutations were inferred by recursively applying a non-linear dimensionality reduction procedure to the mRNA profile data. The resulting static network model accurately predicted 23 of 25 regulatory relationships reported in the literature, suggesting that predictions of novel regulatory relationships are also accurate. The network model revealed two striking features: (i) the components of the network are highly interconnected; and (ii) negative regulatory relationships are common between signaling sectors. Complex regulatory relationships, including a novel negative regulatory relationship between the early microbe-associated molecular pattern-triggered signaling sectors and the salicylic acid sector, were further validated. We propose that prevalent negative regulatory relationships among the signaling sectors make the plant immune signaling network a “sector-switching” network, which effectively balances two apparently conflicting demands, robustness against pathogenic perturbations and moderation of negative impacts of immune responses on plant fitness.


Vyšlo v časopise: Network Modeling Reveals Prevalent Negative Regulatory Relationships between Signaling Sectors in Arabidopsis Immune Signaling. PLoS Pathog 6(7): e32767. doi:10.1371/journal.ppat.1001011
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1001011

Souhrn

Biological signaling processes may be mediated by complex networks in which network components and network sectors interact with each other in complex ways. Studies of complex networks benefit from approaches in which the roles of individual components are considered in the context of the network. The plant immune signaling network, which controls inducible responses to pathogen attack, is such a complex network. We studied the Arabidopsis immune signaling network upon challenge with a strain of the bacterial pathogen Pseudomonas syringae expressing the effector protein AvrRpt2 (Pto DC3000 AvrRpt2). This bacterial strain feeds multiple inputs into the signaling network, allowing many parts of the network to be activated at once. mRNA profiles for 571 immune response genes of 22 Arabidopsis immunity mutants and wild type were collected 6 hours after inoculation with Pto DC3000 AvrRpt2. The mRNA profiles were analyzed as detailed descriptions of changes in the network state resulting from the genetic perturbations. Regulatory relationships among the genes corresponding to the mutations were inferred by recursively applying a non-linear dimensionality reduction procedure to the mRNA profile data. The resulting static network model accurately predicted 23 of 25 regulatory relationships reported in the literature, suggesting that predictions of novel regulatory relationships are also accurate. The network model revealed two striking features: (i) the components of the network are highly interconnected; and (ii) negative regulatory relationships are common between signaling sectors. Complex regulatory relationships, including a novel negative regulatory relationship between the early microbe-associated molecular pattern-triggered signaling sectors and the salicylic acid sector, were further validated. We propose that prevalent negative regulatory relationships among the signaling sectors make the plant immune signaling network a “sector-switching” network, which effectively balances two apparently conflicting demands, robustness against pathogenic perturbations and moderation of negative impacts of immune responses on plant fitness.


Zdroje

1. Bar-YamY

HarmonD

de BivortB

2009 Systems biology. Attractors and democratic dynamics. Science 323 1016 1017

2. KitanoH

2002 Systems biology: a brief overview. Science 295 1662 1664

3. JonesJD

DanglJL

2006 The plant immune system. Nature 444 323 329

4. Gómez-GómezL

BollerT

2000 FLS2: an LRR receptor-like kinase involved in the perception of the bacterial elicitor flagellin in Arabidopsis. Mol Cell 5 1003 1011

5. BlockA

LiG

FuZQ

AlfanoJR

2008 Phytopathogen type III effector weaponry and their plant targets. Curr Opin Plant Biol 11 396 403

6. AxtellMJ

StaskawiczBJ

2003 Initiation of RPS2-specified disease resistance in Arabidopsis is coupled to the AvrRpt2-directed elimination of RIN4. Cell 112 369 377

7. MackeyD

BelkhadirY

AlonsoJM

EckerJR

DanglJL

2003 Arabidopsis RIN4 is a target of the type III virulence effector AvrRpt2 and modulates RPS2-mediated resistance. Cell 112 379 389

8. UnderwoodW

ZhangS

HeSY

2007 The Pseudomonas syringae type III effector tyrosine phosphatase HopAO1 suppresses innate immunity in Arabidopsis thaliana. Plant J 52 658 672

9. TorresMA

DanglJL

JonesJD

2002 Arabidopsis gp91phox homologues AtrbohD and AtrbohF are required for accumulation of reactive oxygen intermediates in the plant defense response. Proc Natl Acad Sci USA 99 517 522

10. ZhangJ

ShaoF

LiY

CuiH

ChenL

2007 A Pseudomonas syringae effector inactivates MAPKs to suppress PAMP-induced immunity in plants. Cell Host Microbe 1 175 185

11. ZeierJ

DelledonneM

MishinaT

SeveriE

SonodaM

2004 Genetic elucidation of nitric oxide signaling in incompatible plant-pathogen interactions. Plant Physiol 136 2875 2886

12. ZeidlerD

ZähringerU

GerberI

DuberyI

HartungT

2004 Innate immunity in Arabidopsis thaliana: lipopolysaccharides activate nitric oxide synthase (NOS) and induce defense genes. Proc Natl Acad Sci USA 101 15811 15816

13. NavarroL

ZipfelC

RowlandO

KellerI

RobatzekS

2004 The transcriptional innate immune response to flg22. Interplay and overlap with Avr gene-dependent defense responses and bacterial pathogenesis. Plant Physiol 135 1113 1128

14. LoakeG

GrantM

2007 Salicylic acid in plant defence–the players and protagonists. Curr Opin Plant Biol 10 466 472

15. PozoMJ

Van LoonLC

PieterseCM

2004 Jasmonates - Signals in Plant-Microbe Interactions. Journal of Plant Growth and Regulation 23 211 222

16. van LoonLC

GeraatsBP

LinthorstHJ

2006 Ethylene as a modulator of disease resistance in plants. Trends Plant Sci 11 184 191

17. WildermuthMC

DewdneyJ

WuG

AusubelFM

2001 Isochorismate synthase is required to synthesize salicylic acid for plant defence. Nature 414 562 565

18. NawrathC

HeckS

ParinthawongN

MétrauxJP

2002 EDS5, an essential component of salicylic acid-dependent signaling for disease resistance in Arabidopsis, is a member of the MATE transporter family. Plant Cell 14 275 286

19. CaoH

GlazebrookJ

ClarkeJD

VolkoS

DongX

1997 The Arabidopsis NPR1 gene that controls systemic acquired resistance encodes a novel protein containing ankyrin repeats. Cell 88 57 63

20. FalkA

FeysBJ

FrostLN

JonesJD

DanielsMJ

1999 EDS1, an essential component of R gene-mediated disease resistance in Arabidopsis has homology to eukaryotic lipases. Proc Natl Acad Sci USA 96 3292 3297

21. JirageD

TootleTL

ReuberTL

FrostLN

FeysBJ

1999 Arabidopsis thaliana PAD4 encodes a lipase-like gene that is important for salicylic acid signaling. Proc Natl Acad Sci USA 96 13583 13588

22. GlazebrookJ

ChenW

EstesB

ChangHS

NawrathC

2003 Topology of the network integrating salicylate and jasmonate signal transduction derived from global expression phenotyping. Plant J 34 217 228

23. StaswickPE

TiryakiI

RoweML

2002 Jasmonate response locus JAR1 and several related Arabidopsis genes encode enzymes of the firefly luciferase superfamily that show activity on jasmonic, salicylic, and indole-3-acetic acids in an assay for adenylation. Plant Cell 14 1405 1415

24. ThinesB

KatsirL

MelottoM

NiuY

MandaokarA

2007 JAZ repressor proteins are targets of the SCF(COI1) complex during jasmonate signalling. Nature 448 661 665

25. LorenzoO

ChicoJM

Sánchez-SerranoJJ

SolanoR

2004 JASMONATE-INSENSITIVE1 encodes a MYC transcription factor essential to discriminate between different jasmonate-regulated defense responses in Arabidopsis. Plant Cell 16 1938 1950

26. AlonsoJM

HirayamaT

RomanG

NourizadehS

EckerJR

1999 EIN2, a bifunctional transducer of ethylene and stress responses in Arabidopsis. Science 284 2148 2152

27. ChaoQ

RothenbergM

SolanoR

RomanG

TerzaghiW

1997 Activation of the ethylene gas response pathway in Arabidopsis by the nuclear protein ETHYLENE-INSENSITIVE3 and related proteins. Cell 89 1133 1144

28. Robert-SeilaniantzA

NavarroL

BariR

JonesJD

2007 Pathological hormone imbalances. Curr Opin Plant Biol 10 372 379

29. ZipfelC

RobatzekS

NavarroL

OakeleyEJ

JonesJD

2004 Bacterial disease resistance in Arabidopsis through flagellin perception. Nature 428 764 767

30. TsudaK

SatoM

GlazebrookJ

CohenJD

KatagiriF

2008 Interplay between MAMP-triggered and SA-mediated defense responses. Plant J 53 763 775

31. TsudaK

SatoM

StoddardT

GlazebrookJ

KatagiriF

2009 Network properties of robust immunity in plants. PLoS Genet 5 e1000772

32. HughesTR

MartonMJ

JonesAR

RobertsCJ

StoughtonR

2000 Functional discovery via a compendium of expression profiles. Cell 102 109 126

33. RoweisST

SaulLK

2000 Nonlinear dimensionality reduction by locally linear embedding. Science 290 2323 2326

34. KatagiriF

GlazebrookJ

2003 Local Context Finder (LCF) reveals multidimensional relationships among mRNA expression profiles of Arabidopsis responding to pathogen infection. Proc Natl Acad Sci USA 100 10842 10847

35. van LeeuwenH

KliebensteinDJ

WestMA

KimK

van PoeckeR

2007 Natural variation among Arabidopsis thaliana accessions for transcriptome response to exogenous salicylic acid. Plant Cell 19 2099 2110

36. Van PoeckeRM

SatoM

Lenarz-WyattL

WeisbergS

KatagiriF

2007 Natural variation in RPS2-mediated resistance among Arabidopsis accessions: correlation between gene expression profiles and phenotypic responses. Plant Cell 19 4046 4060

37. SatoM

MitraRM

CollerJ

WangD

SpiveyNW

2007 A high-performance, small-scale microarray for expression profiling of many samples in Arabidopsis-pathogen studies. Plant J 49 565 577

38. DelledonneM

XiaY

DixonRA

LambC

1998 Nitric oxide functions as a signal in plant disease resistance. Nature 394 585 588

39. GlazebrookJ

2005 Contrasting mechanisms of defense against biotrophic and necrotrophic pathogens. Annu Rev Phytopathol 43 205 227

40. DanglJL

JonesJD

2001 Plant pathogens and integrated defence responses to infection. Nature 411 826 833

41. HeP

ChintamananiS

ChenZ

ZhuL

KunkelBN

2004 Activation of a COI1-dependent pathway in Arabidopsis by Pseudomonas syringae type III effectors and coronatine. Plant J 37 589 602

42. Gómez-GómezL

FelixG

BollerT

1999 A single locus determines sensitivity to bacterial flagellin in Arabidopsis thaliana. Plant J 18 277 284

43. AsaiT

TenaG

PlotnikovaJ

WillmannMR

ChiuWL

2002 MAP kinase signalling cascade in Arabidopsis innate immunity. Nature 415 977 983

44. BauerZ

Gómez-GómezL

BollerT

FelixG

2001 Sensitivity of different ecotypes and mutants of Arabidopsis thaliana toward the bacterial elicitor flagellin correlates with the presence of receptor-binding sites. J Biol Chem 276 45669 45676

45. ClayNK

AdioAM

DenouxC

JanderG

AusubelFM

2009 Glucosinolate metabolites required for an Arabidopsis innate immune response. Science 323 95 101

46. TaoY

XieZ

ChenW

GlazebrookJ

ChangHS

2003 Quantitative nature of Arabidopsis responses during compatible and incompatible interactions with the bacterial pathogen Pseudomonas syringae. Plant Cell 15 317 330

47. TakahashiF

YoshidaR

IchimuraK

MizoguchiT

SeoS

2007 The mitogen-activated protein kinase cascade MKK3-MPK6 is an important part of the jasmonate signal transduction pathway in Arabidopsis. Plant Cell 19 805 818

48. ChenH

XueL

ChintamananiS

GermainH

LinH

2009 ETHYLENE INSENSITIVE3 and ETHYLENE INSENSITIVE3-LIKE1 repress SALICYLIC ACID INDUCTION DEFICIENT2 expression to negatively regulate plant innate immunity in Arabidopsis. Plant Cell 21 2527 2540

49. YooSD

ChoYH

TenaG

XiongY

SheenJ

2008 Dual control of nuclear EIN3 by bifurcate MAPK cascades in C2H4 signalling. Nature 451 789 795

50. ZottiniM

CostaA

De MicheleR

RuzzeneM

CarimiF

2007 Salicylic acid activates nitric oxide synthesis in Arabidopsis. J Exp Bot 58 1397 1405

51. NawrathC

MétrauxJP

1999 Salicylic acid induction-deficient mutants of Arabidopsis express PR-2 and PR-5 and accumulate high levels of camalexin after pathogen inoculation. Plant Cell 11 1393 1404

52. NishimuraMT

SteinM

HouBH

VogelJP

EdwardsH

2003 Loss of a callose synthase results in salicylic acid-dependent disease resistance. Science 301 969 972

53. HamJH

KimMG

LeeSY

MackeyD

2007 Layered basal defenses underlie non-host resistance of Arabidopsis to Pseudomonas syringae pv. phaseolicola. Plant J 51 604 616

54. JacobsAK

LipkaV

BurtonRA

PanstrugaR

StrizhovN

2003 An Arabidopsis Callose Synthase, GSL5, Is Required for Wound and Papillary Callose Formation. Plant Cell 15 2503 2513

55. DenouxC

GallettiR

MammarellaN

GopalanS

WerckD

2008 Activation of Defense Response Pathways by OGs and Flg22 Elicitors in Arabidopsis Seedlings. Mol Plant 1 423 445

56. ShangY

LiX

CuiH

HeP

ThilmonyR

2006 RAR1, a central player in plant immunity, is targeted by Pseudomonas syringae effector AvrB. Proc Natl Acad Sci USA 103 19200 19205

57. LambJ

CrawfordED

PeckD

ModellJW

BlatIC

2006 The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease. Science 313 1929 1935

58. DongX

2004 NPR1, all things considered. Curr Opin Plant Biol 7 547 552

59. TohH

HorimotoK

2002 Inference of a genetic network by a combined approach of cluster analysis and graphical Gaussian modeling. Bioinformatics 18 287 297

60. BoltonMD

2009 Primary metabolism and plant defense–fuel for the fire. Mol Plant Microbe Interact 22 487 497

61. BowlingSA

ClarkeJD

LiuY

KlessigDF

DongX

1997 The cpr5 mutant of Arabidopsis expresses both NPR1-dependent and NPR1-independent resistance. Plant Cell 9 1573 1584

62. ClarkeJD

LiuY

KlessigDF

DongX

1998 Uncoupling PR gene expression from NPR1 and bacterial resistance: characterization of the dominant Arabidopsis cpr6-1 mutant. Plant Cell 10 557 569

63. TianD

TrawMB

ChenJQ

KreitmanM

BergelsonJ

2003 Fitness costs of R-gene-mediated resistance in Arabidopsis thaliana. Nature 423 74 77

64. SpoelSH

KoornneefA

ClaessensSM

KorzeliusJP

Van PeltJA

2003 NPR1 modulates cross-talk between salicylate- and jasmonate-dependent defense pathways through a novel function in the cytosol. Plant Cell 15 760 770

65. WhalenMC

InnesRW

BentAF

StaskawiczBJ

1991 Identification of Pseudomonas syringae pathogens of Arabidopsis and a bacterial locus determining avirulence on both Arabidopsis and soybean. Plant Cell 3 49 59

66. KatagiriF

ThilmonyR

HeSY

2002 The Arabidopsis Thaliana-Pseudomonas Syringae Interaction The Arabidopsis Book 1 35

67. BenjaminiY

HochbergY

1995 Controlling the False Discovery Rate: a Practical and Powerful Approach to Multiple Testing. Journal of the Royal Statistical Society B 57 289 300

68. WangL

TsudaK

SatoM

CohenJD

KatagiriF

2009 Arabidopsis CaM binding protein CBP60g contributes to MAMP-induced SA accumulation and is involved in disease resistance against Pseudomonas syringae. PLoS Pathog 5 e1000301

69. TrujilloM

IchimuraK

CasaisC

ShirasuK

2008 Negative regulation of PAMP-triggered immunity by an E3 ubiquitin ligase triplet in Arabidopsis. Curr Biol 18 1396 1401

70. ShahJ

2003 The salicylic acid loop in plant defense. Curr Opin Plant Biol 6 365 371

71. GuoFQ

OkamotoM

CrawfordNM

2003 Identification of a plant nitric oxide synthase gene involved in hormonal signaling. Science 302 100 103

72. TorresMA

OnouchiH

HamadaS

MachidaC

Hammond-KosackKE

1998 Six Arabidopsis thaliana homologues of the human respiratory burst oxidase (gp91phox). Plant J 14 365 370

73. XieDX

FeysBF

JamesS

Nieto-RostroM

TurnerJG

1998 COI1: an Arabidopsis gene required for jasmonate-regulated defense and fertility. Science 280 1091 1094

74. ParkJH

HalitschkeR

KimHB

BaldwinIT

FeldmannKA

2002 A knock-out mutation in allene oxide synthase results in male sterility and defective wound signal transduction in Arabidopsis due to a block in jasmonic acid biosynthesis. Plant J 31 1 12

75. WangH

NgwenyamaN

LiuY

WalkerJC

ZhangS

2007 Stomatal development and patterning are regulated by environmentally responsive mitogen-activated protein kinases in Arabidopsis. Plant Cell 19 63 73

76. LiuY

ZhangS

2004 Phosphorylation of 1-aminocyclopropane-1-carboxylic acid synthase by MPK6, a stress-responsive mitogen-activated protein kinase, induces ethylene biosynthesis in Arabidopsis. Plant Cell 16 3386 3399

77. KangL

LiJ

ZhaoT

XiaoF

TangX

2003 Interplay of the Arabidopsis nonhost resistance gene NHO1 with bacterial virulence. Proc Natl Acad Sci U S A 100 3519 3524

78. WilkinsonJQ

CrawfordNM

1991 Identification of the Arabidopsis CHL3 gene as the nitrate reductase structural gene NIA2. Plant Cell 3 461 471

79. CenturyKS

ShapiroAD

RepettiPP

DahlbeckD

HolubE

1997 NDR1, a pathogen-induced component required for Arabidopsis disease resistance. Science 278 1963 1965

80. WarrenRF

MerrittPM

HolubE

InnesRW

1999 Identification of three putative signal transduction genes involved in R gene-specified disease resistance in Arabidopsis. Genetics 152 401 412

81. TorneroP

MerrittP

SadanandomA

ShirasuK

InnesRW

2002 RAR1 and NDR1 contribute quantitatively to disease resistance in Arabidopsis, and their relative contributions are dependent on the R gene assayed. Plant Cell 14 1005 1015

82. LipkaV

DittgenJ

BednarekP

BhatR

WiermerM

2005 Pre- and postinvasion defenses both contribute to nonhost resistance in Arabidopsis. Science 310 1180 1183

83. BentAF

KunkelBN

DahlbeckD

BrownKL

SchmidtR

1994 RPS2 of Arabidopsis thaliana: a leucine-rich repeat class of plant disease resistance genes. Science 265 1856 1860

84. MindrinosM

KatagiriF

YuGL

AusubelFM

1994 The A. thaliana disease resistance gene RPS2 encodes a protein containing a nucleotide-binding site and leucine-rich repeats. Cell 78 1089 1099

85. FeysBJ

WiermerM

BhatRA

MoisanLJ

Medina-EscobarN

2005 Arabidopsis SENESCENCE-ASSOCIATED GENE101 stabilizes and signals within an ENHANCED DISEASE SUSCEPTIBILITY1 complex in plant innate immunity. Plant Cell 17 2601 2613

86. Lozano-JusteJ

LeónJ

2010 Enhanced abscisic acid-mediated responses in nia1nia2noa1-2 triple mutant impaired in NIA/NR- and AtNOA1-dependent nitric oxide biosynthesis in Arabidopsis. Plant Physiol 152 891 903

87. GfellerA

LiechtiR

FarmerEE

2010 Arabidopsis jasmonate signaling pathway. Science signaling 3 cm4

88. LaudertD

WeilerEW

1998 Allene oxide synthase: a major control point in Arabidopsis thaliana octadecanoid signalling. Plant J 15 675 684

89. RomanG

LubarskyB

KieberJJ

RothenbergM

EckerJR

1995 Genetic analysis of ethylene signal transduction in Arabidopsis thaliana: five novel mutant loci integrated into a stress response pathway. Genetics 139 1393 1409

90. ChiniA

FonsecaS

FernándezG

AdieB

ChicoJM

2007 The JAZ family of repressors is the missing link in jasmonate signalling. Nature 448 666 671

91. YanY

StolzS

ChételatA

ReymondP

PagniM

2007 A downstream mediator in the growth repression limb of the jasmonate pathway. Plant Cell 19 2470 2483

92. Laurie-BerryN

JoardarV

StreetIH

KunkelBN

2006 The Arabidopsis thaliana JASMONATE INSENSITIVE 1 gene is required for suppression of salicylic acid-dependent defenses during infection by Pseudomonas syringae. Mol Plant Microbe Interact 19 789 800

93. BrightJ

DesikanR

HancockJT

WeirIS

NeillSJ

2006 ABA-induced NO generation and stomatal closure in Arabidopsis are dependent on H2O2 synthesis. Plant J 45 113 122

94. CaoH

BowlingSA

GordonAS

DongX

1994 Characterization of an Arabidopsis Mutant That Is Nonresponsive to Inducers of Systemic Acquired Resistance. Plant Cell 6 1583 1592

95. ZhouN

TootleTL

TsuiF

KlessigDF

GlazebrookJ

1998 PAD4 functions upstream from salicylic acid to control defense responses in Arabidopsis. Plant Cell 10 1021 1030

96. BelkhadirY

NimchukZ

HubertDA

MackeyD

DanglJL

2004 Arabidopsis RIN4 negatively regulates disease resistance mediated by RPS2 and RPM1 downstream or independent of the NDR1 signal modulator and is not required for the virulence functions of bacterial type III effectors AvrRpt2 or AvrRpm1. Plant Cell 16 2822 2835

97. WangL

MitraRM

HasselmannKD

SatoM

Lenarz-WyattL

2008 The Genetic Network Controlling the Arabidopsis Transcriptional Response to Pseudomonas syringae pv. maculicola: Roles of Major Regulators and the Phytotoxin Coronatine. Mol Plant Microbe Interact 21 1408 1420

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