Abstract
Cell death and disease resistance are intimately connected in plants. Plant disease resistance genes (R genes) are key components in pathogen perception and have a potential to activate cell death pathways. Analysis of R proteins suggests common molecular mechanisms for pathogen recognition and signal emission whereas the subsequent signalling unexpectedly involves a network of pathways of parallel, branching and converging action. Disease resistance signalling mutants have revealed novel types of regulatory proteins whose biochemical functions are still unknown. Accumulation of small molecules such as salicylic acid, reactive oxygen intermediates, and nitric oxide amplifies resistance responses and directs cells to initiate cell death programs. Genetic analyses of lesion mimic mutants provide a glimpse of how cell death thresholds are set via an interplay of positive and negative regulatory components.
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Aarts, N., Metz, M., Holub, E., Staskawicz, B.J., Daniels, M.J. and Parker, J.E. 1998. Different requirements for EDS1 and NDR1 by disease resistance genes define at least two R gene-mediated signaling pathways in Arabidopsis. Proc. Natl. Acad. Sci. USA 95: 10306–10311.
Adams, S.E., Jones, R.A.C. and Coutts, R.H.A. 1986. Expression of potato virus X resistance gene Rx in potato leaf protoplasts. J. Gen. Virol. 67: 2341–2345.
Aravind, L., Dixit, V.M. and Koonin, E.V. 1999. The domains of death: evolution of the apoptosis machinary. Trends Biochem. Sci. 24: 47–53.
Baker, B., Zambryski, P., Staskawicz, B. and Dinesh-Kumar, S.P. 1997. Signaling in plant-microbe interactions. Science 276: 726–733.
Bendahmane, A., Kanyuka, K. and Baulcombe, D.C. 1999. The Rx gene from potato controls separate virus resistance and cell death responses. Plant Cell 11: 781–791.
Bertin, J., Nir, W.J., Fischer, C.M., Tayber, O.V., Errada, P.R., Grant, J.R., Keilty, J.J., Gosselin, M.L., Robison, K.E., Wong, G.H.W., Glucksmann, M.A. and DiStefano, P.S. 1999. Human CARD4 protein is a novel CED-4/Apaf-1 cell death family member that activates NF-kB. J. Biol. Chem. 274: 12955–12958.
Bockaert, J. and Pin, J.P. 1999. Molecular tinkering of G proteincoupled receptors: an evolutionary success. EMBO J. 18: 1723–1729.
Bokoch, G.M. 1994. Regulation of the human neutrophil NADPH oxidase by the Rac GTP-binding proteins. Curr. Opin. Cell Biol. 6: 212–218.
Bradley, D.J., Kjellbom, P. and Lamb, C.J. 1992. Elicitor-induced and wound-induced oxidative cross-linking of a proline-rich plant-cell wall protein: a novel, rapid defense response. Cell 70: 21–30.
Buschges, R., Hollricher, K., Panstruga, R., Simons, G., Wolter, M., Frijters, A., van Daelen, R., van der Lee, T., Diergaarde, P., Groenendijk, J., Topsch, S., Vos, P., Salamini, F. and Schulze-Lefert, P. 1997. The barley Mlo gene: a novel control element of plant pathogen resistance. Cell 88: 695–705.
Century, K.S., Holub, E.B. and Staskawicz, B.J. 1995. NDR1, a locus of Arabidopsis thaliana that is required for disease resistance to both a bacterial and a fungal pathogen. Proc. Natl. Acad. Sci. USA 92: 6597–6601.
Century, K.S., Shapiro, A.D., Repetti, P.P., Dahlbeck, D., Holub, E. and Staskawicz, B.J. 1997. NDR1, a pathogen-induced component required for Arabidopsis disease resistance. Science 278: 1963–1965.
Chandra, S., Martin, G.B. and Low, P.S. 1996. The Pto kinase mediates a signaling pathway leading to the oxidative burst in tomato. Proc. Natl. Acad. Sci. USA 93: 13393–13397.
Chinnaiyan, A.M., Chaudhary, D., Orourke, K., Koonin, E.V. and Dixit, V.M. 1997. Role of CED-4 in the activation of CED-3. Nature 388: 728–729.
Delaney, T.P., Uknes, S., Vernooij, B., Friedrich, L., Weymann, K., Negrotto, D., Gaffney, T., Gutrella, M., Kessmann, H., Ward, E. and Ryals, J. 1994. A central role of salicylic acid in plantdisease resistance. Science 266: 1247–1250.
Delledonne, M., Xia, Y.J., Dixon, R.A. and Lamb, C. 1998. Nitric oxide functions as a signal in plant disease resistance. Nature 394: 585–588.
Devoto, A., Piffanelli, P., Nilsson, I., Wallin, E., Panstruga, R., von Heijne, G. and Schulze-Lefert P. 1999. Topology, subcellular localization and sequence diversity of the Mlo family in plants. J. Biol. Chem. 274: 34993–35004.
Dietrich, R.A., Delaney, T.P., Uknes, S.J., Ward, E.R., Ryals, J.A. and Dangl, J.L. 1994. Arabidopsis mutants simulating disease resistance response. Cell 77: 565–577.
Dietrich, R.A., Richberg, M.H., Schmidt, R., Dean, C. and Dangl, J.L. 1997. A novel zinc finger protein is encoded by the Arabidopsis LSD1 gene and functions as a negative regulator of plant cell death. Cell 88: 685–694.
Doke, N. 1985. NADPH-dependent O2 _generation in membrane fraction isolated from wounded potato tubers inoculated with Phytophthora infestans. Physiol. Plant Path. 27: 311–322.
Draper, J. 1997. Salicylate, superoxide synthesis and cell suicide in plant defence. Trends Plant Sci. 2: 162–165.
Durner, J., Wendehenne, D. and Klessig, D.F. 1998. Defense gene induction in tobacco by nitric oxide, cyclic GMP, and cyclic ADP-ribose. Proc. Natl. Acad. Sci. USA 95: 10328–10333.
Ellis, J. and Jones, D. 1998. Structure and function of proteins controlling strain-specific pathogen resistance in plants. Curr. Opin. Plant Biol. 1: 288–293.
Ellis, J.G., Lawrence, G.J., Luck, J.E. and Dodds, P.N. 1999. Identification of regions in alleles of the flax rust resistance gene L that determine differences in gene-for-gene specificity. Plant Cell 11: 495–506.
Falk, A., Feys, B.J., Frost, L.N., Jones, J.D.G., Daniels, M.J. and Parker, J.E. 1999. EDS1, an essential component of R genemediated disease resistance in Arabidopsis has homology to eukaryotic lipases. Proc. Natl. Acad. Sci. USA 96: 3292–3297.
Flor, H.H. 1971. Current status of the gene-for-gene concept. Annu. Rev. Phytopath. 9: 275–296.
Freialdenhoven, A., Scherag, B., Hollricher, K., Collinge, D.B., Thordal-Christensen, H. and Schulze-Lefert, P. 1994. Nar-1 and Nar-2, two loci required for Mla12-specified race-specific resistance to powdery mildew in barley. Plant Cell 6: 983–994.
Freialdenhoven, A., Peterhänsel, C., Kurth, J., Kreuzaler, F. and Schulze-Lefert, P. 1996. Identification of genes required for the function of non-race-specific mlo resistance to powdery mildew in barley. Plant Cell 8: 5–14.
Frye, C.A. and Innes, R.W. 1998. An Arabidopsis mutant with enhanced resistance to powdery mildew. Plant Cell 10: 947–956.
Gaffney, T., Friedrich, L., Vernooij, B., Negrotto, D., Nye, G., Uknes, S., Ward, E., Kessmann, H. and Ryals, J. 1993. Requirement of salicylic acid for the induction of systemic acquired resistance. Science 261: 754–756.
Gaullier, J.M., Simonsen, A., Darrigo, A., Bremnes, B., Stenmark, H. and Aasland, R. 1998. FYVE fingers bind Ptdins(3)P. Nature 394: 432–433.
Gopalan, S., Wei, W. and He, S.Y. 1996. hrp gene-dependent induction of hin1: a plant gene activated rapidly by both harpins and the avrPto gene-mediated signal. Plant J. 10: 591–600.
Görg, R., Hollricher, K. and Schulze-Lefert, P. 1993. Functional analysis and RFLP-mediated mapping of the Mlg resistance locus in barley. Plant J. 3: 857–866.
Gray, J., Close, P.S., Briggs, S.P. and Johal, G.S. 1997. A novel suppressor of cell death in plants encoded by the Lls1 gene of maize. Cell 89: 25–31.
Greenberg, J.T. and Ausubel, F.M. 1993. Arabidopsis mutants compromised for the control of cellular damage during pathogenesis and aging. Plant J. 4: 327–341.
Gumienny, T.L., Lambie, E., Hartwieg, E., Horvitz, H.R. and Hengartner, M.O. 1998. Genetic control of programmed cell death in the Caenorhabditis elegans hermaphrodite germline. Development 126: 1011–1022.
Hammond-Kosack, K.E. and Jones, J.D.G. 1994. Incomplete dominance of tomato Cf genes for resistance to Cladosporium fulvum. Mol. Plant-Microbe Interact. 7: 58–70.
Hammond-Kosack, K.E., Staskawicz, B.J., Jones, J.D.G. and Baulcombe, D.C. 1995. Functional expression of a fungal avirulence gene from a modified potato virus X genome. Mol. Plant-Microbe Interact. 8: 181–185.
Hoisington, D.A., Neuffer, M.G. and Walbot, V. 1982. Disease lesion mimics in maize. 1. Effect of genetic background, temperature, developmental age, and wounding on necrotic spot formation with Les1. Dev. Biol. 93: 381–388.
Hu, G., Richter, T.E., Hulbert, S.H. and Pryor, T. 1996. Disease lesion mimicry caused by mutations in the rust resistance gene rp1. Plant Cell 8: 1367–1376.
Hu, G.S., Yalpani, N., Briggs, S.P. and Johal, G.S. 1998. A porphyrin pathway impairment is responsible for the phenotype of a dominant disease lesion mimic mutant of maize. Plant Cell 10: 1095–1105.
Hückelhoven, R. and Kogel, K.-H. 1998. Tissue-specific superoxide generation at interaction sites in resistant and susceptible nearisogenic barley lines attacked by the powdery mildew fungus (Erysiphe graminis f.sp. hordei). Mol. Plant-Microbe Interact. 11: 292–300.
Hunt, M.D., Delaney, T.P., Dietrich, R.A., Weymann, K.B., Dangl, J.L. and Ryals, J.A. 1997. Salicylate-independent lesion formation in Arabidopsis lsd mutants. Mol. Plant-Microbe Interact. 10: 531–536.
Jabs, T., Dietrich, R.A. and Dangl, J.L. 1996. Initiation of runaway cell death in an Arabidopsis mutant by extracellular superoxide. Science 273: 1853–1856.
Jarosch, B., Kogel, K.H. and Schaffrath, U. 1999. The ambivalence of the barley Mlo locus: mutations conferring resistance against powdery mildew (Blumeria graminis f. sp. hordei) enhance susceptibility to the rice blast fungus Magnaporthe grisea. Mol. Plant-Microbe Interact. 12: 508–514.
Jones, D.A., Thomas, C.M., Hammond-Kosack, K.E., Balint-Kurti, P.J. and Jones, J.D.G. 1994. Isolation of the tomato Cf-9 gene for resistance to Cladosporium fulvum by transposon tagging. Science 266: 789–793.
Jø rgensen, J.H. 1988. Genetic-analysis of barley mutants with modifications of powdery mildew resistance gene Ml-a12. Genome 30: 129–132.
Jø rgensen, J.H. 1996. Effect of three suppressors on the expression of powdery mildew resistance genes in barley. Genome 39: 492–498.
Kawasaki, T., Henmi, K., Ono, E., Hatakeyama, S., Iwano, M., Satoh, H. and Shimamoto, K. 1999. The small GTP-binding protein Rac is a regulator of cell death in plants. Proc. Natl. Acad. Sci. USA 96: 10922–10926.
Keller, T., Damude, H.G., Werner, D., Doerner, P., Dixon, R.A. and Lamb, C. 1998. A plant homolog of the neutrophil NADPH oxidase gp91phox subunit gene encodes a plasma membrane protein with Ca2+ binding motifs. Plant Cell 10: 255–266.
Klement, Z. 1963. Rapid detection of the pathogenicity of phytopathogenic pseudomonads. Nature 199: 299–300.
Klement, Z. 1982. Hypersensitivity. In: Phytopathogenic Prokaryotes, Academic Press, New York, pp. 149–177.
Kobe, B. and Deisenhofer, J. 1995. A structural basis of the interactions between leucine-rich repeats and protein ligands. Nature 366: 183–186.
Köhm, B.A., Goulden, M.G., Gilbert, J.E., Kavanagh, T.A. and Baulcombe, D.C. 1993. A potato virus X resistance gene mediates an induced, nonspecific resistance in protoplasts. Plant Cell 5: 913–920.
Lamb, C. and Dixon, R.A. 1997. The oxidative burst in plant disease resistance. Annu. Rev. Plant Physiol Plant Mol. Biol. 48: 251–275.
Lebrun, M.H., Dutfoy, F., Gaudemer, F., Kunesch, G. and Gaudemer, A. 1990. Detection and quantification of the fungal phytotoxin tenuazonic acid produced by Pyricularia oryzae. Phytochemistry 29: 3777–3783.
Leckie, F., Mattei, B., Capodicasa, C., Hemmings, A., Nuss, L., Aracri, B., DeLorenzo, G. and Cervone, F. 1999. The specificity of polygalacturonase-inhibiting protein (PGIP): a single amino acid substitution in the solvent-exposed β-strand/β-turn region of the leucine-rich repeats (LRRs) confers a new recognition capability. EMBO J. 18: 2352–2363.
Levine, A., Tenhaken, R., Dixon, R. and Lamb, C. 1994. H2O2 from the oxidative burst orchestrates the plant hypersensitive disease resistance response. Cell 79: 583–593.
Martin, G.B., Brommonschenkel, S.H., Chungwongse, J., Frary, A., Ganal, M.W., Spivey, R., Wu, T., Earle, E.D. and Tanksley, S.D. 1993. Map-based cloning of a protein kinase gene conferring disease resistance in tomato. Science 262: 1432–1436.
Molina, A., Volrath, S., Guyer, D., Maleck, K., Ryals, J. and Ward, E. 1999. Inhibition of protoporphyrinogen oxidase expression in Arabidopsis causes a lesion-mimic phenotype that induces systemic acquired resistance. Plant J. 17: 667–678.
Olie, R.A., Durrieu, F., Cornillon, S., Loughran, G., Gross, J., Earnshaw, W.C. and Golstein, P. 1998. Apparent caspase independence of programmed cell death in Dictyostelium. Curr. Biol. 8: 955–958.
Parker, J.E., Holub, E.B., Frost, L.N., Falk, A., Gunn, N.D. and Daniels, M.J. 1996. Characterization of eds1, a mutation in Arabidopsis suppressing resistance to Peronospora parasitica specified by several different RPP genes. Plant Cell 8: 2033–2046.
Parniske, M., Hammond-Kosack, K.E., Golstein, C., Thomas, C.M., Jones, D.A., Harrison, K., Wulff, B.B.H. and Jones, J.D.G. 1997. Novel disease resistance specificities result from sequence exchange between tandemly repeated genes at the Cf-4/9 locus of tomato. Cell 91: 821–832.
Peterhänsel, C., Freialdenhoven, A., Kurth, J., Kolsch, R. and Schulze-Lefert, P. 1997. Interaction analyses of genes required for resistance responses to powdery mildew in barley reveal distinct pathways leading to leaf cell death. Plant Cell 9: 1397–1409.
Pontier, D., Gan, S., Amasino, R.M., Robby, D. and Lam, E. 1999. Markers for hypersensitive response and senescence show distinct patterns of expression. Plant Mol. Biol. 39: 1243–1255.
Rao, M.V. and Davis, K.R. 1999. Ozone-induced cell death occurs via two distinct mechanisms in Arabidopsis: the role of salicylic acid. Plant J. 17: 603–614.
Rate, D.N., Cuenca, J.V., Bowman, G.R., Guttman, D.S. and Greenberg, J.T. 1999. The gain-of-function Arabidopsis acd6 mutant reveals novel regulation and function of the salicylic acid signaling pathway in controlling cell death, defenses, and cell growth. Plant Cell 11: 1695–1708.
Rathjen, J.P., Chang, J.H., Staskawicz, B.J. and Michelmore, R.W. 1999. Constitutively active Pto induces a Prf-dependent hypersensitive response in the absence of avrPto. EMBO J. 18: 3232–3240.
Runeckles, V.C. and Vaartnou, M. 1997. EPR evidence for superoxide anion formation in leaves during exposure to low levels of ozone. Plant Cell Envir. 20: 306–314.
Salmeron, J.M., B arker, S.J., Carland, F.M., Mehta, A.Y. and Staskawicz, B.J. 1994. Tomato mutants altered in bacterial disease resistance provide evidence for a new locus controlling pathogen recognition. Plant Cell 6: 511–520.
Salmeron, J.M., Oldroyd, G.E.D., Rommens, C.M.T., Scofield, S.R., Kim, H.S., Lavelle, D.T., Dahlbeck, D. and Staskawicz, B.J. 1996. Tomato Prf is a member of the leucine-rich repeat class of plant disease resistance genes and lies embedded within the Pto kinase gene cluster. Cell 86: 123–133.
Schmidt, H.H.H.W. and Walter, U. 1994. No at work. Cell 78: 919–925.
Scofield, S.R., Tobias, C.M., Rathjen, J.P., Chang, J.H., Lavelle, D.T., Michelmore, R.W. and Staskawicz, B.J. 1996. Molecular basis of gene-for-gene specificity in bacterial speck disease of tomato. Science 274: 2063–2065.
Shah, J., Kachroo, P. and Klessig, D.F. 1999. The Arabidopsis ssi1 mutation restores pathogenesis-related gene expression in npr1 plants and renders defensin gene expression salicylic acid dependent. Plant Cell 11: 191–206.
Sharma, Y.K. and Davis, K.R. 1997. The effects of ozone on antioxidant responses in plants. Free Radical Biol. Med. 23: 480–488.
Shirasu, K., Nakajima, H., Rajasekhar, V.K., Dixon, R.A. and Lamb, C. 1997. Salicylic acid potentiates an agonist-dependent gain control that amplifies pathogen signals in the activation of defense mechanisms. Plant Cell 9: 261–270.
Shirasu, K., Lahaye, L., Tan, M.-W., Zhou, F., Azevedo, C. and Schulze-Lefert, P. 1999a. A novel class of eukaryotic zincbinding protein is required for disease resistance signaling in barley and development in C. elegans. Cell 99: 355–366.
Shirasu, K., Nielsen, K., Piffanelli, P., Oliver, R. and Schulze-Lefert, P. 1999b. Cell-autonomous complementation of mlo resistance using a biolistic transient expression system. Plant J. 17: 293–299.
Simmons, C., Hantke, S., Grant, S., Johal, G.S. and Briggs, S.P. 1998. The maize lethal leaf spot 1 mutant has elevated resistance to fungal infection at the leaf epidermis. Mol. Plant-Microbe Interact. 11: 1110–1118.
Song, W.Y., Wang, G.L., Chen, L.L., Kim, H.S., Pi, L.Y., Holsten, T., Gardner, J., Wang, B., Zhai, W.X., Zhu, L.H., Fauquet, C. and Ronald, P. 1995. A receptor kinase-like protein encoded by the rice disease resistance gene, Xa21. Science 270: 1804–1806.
Stakman, E.C. 1915. Relation between Puccinia graminis and plants highly resistance to its attack. J. Agric. Res. 4: 193–199.
Tang, X.Y., Frederick, R.D., Zhou, J.M., Halterman, D.A., Jia, Y.L. and Martin, G.B. 1996. Initiation of plant disease resistance by physical interaction of AvrPto and Pto kinase. Science 274: 2060–2063.
Thomas, C.M., Jones, D.A., Parniske, M., Harrison, K., Balint-Kurti, P.J., Hatzixanthis, K. and Jones, J.D.G. 1997. Characterization of the tomato Cf-4 gene for resistance to Cladosporium fulvum identifies sequences that determine recognitional specificity in Cf-4 and Cf-9. Plant Cell 9: 2209–2224.
Thordal-Christensen, H., Zhang, Z.G., Wei, Y.D. and Collinge, D.B. 1997. Subcellular localization of H2O2 in plants. H2O2 accumulation in papillae and hypersensitive response during the barley-powdery mildew interaction. Plant J. 11: 1187–1194.
Thornberry, N.A. and Lazebnik, Y. 1998. Caspases: enemies within. Science 281: 1312–1316.
Torp, J. and Jörgensen, J.H. 1986. Modification of barley powdery mildew resistance gene Ml-a12 by induced mutation. Can. J. Gen. Cytol. 28: 725–731.
Torres, M.A., Onouchi, H., Hamada, S., Machida, C., Hammond-Kosack, K.E. and Jones, J.D.G. 1998. Six Arabidopsis thaliana homologues of the human respiratory burst oxidase (gp91phox). Plant J. 14: 365–370.
van den Ackerveken, G.F.J.M., van Kan, J.A.L. and deWit, P.J.G.M. 1992. Molecular analysis of the avirulence gene Avr9 of the fungal tomato pathogen Cladosporium fulvum fully supports the gene-for-gene hypothesis. Plant J. 2: 359–366.
van der Biezen, E.A. and Jones, J.D.G. 1998. The NB-ARC domain: a novel signalling motif shared by plant resistance gene products and regulators of cell death in animals. Curr. Biol. 8: R226–R227.
von Röpenack, E., Parr, A. and Schulze-Lefert, P. 1998. Structural analyses and dynamics of soluble and cell wall-bound phenolics in a broad spectrum resistance to the powdery mildew fungus in barley. J. Biol. Chem. 273: 9013–9022.
Warren, R.F., Merrit, P.M., Holub, E. and Innes, R.W. 1999. Identification of three putative signal transduction genes involved in R gene-specific resistance in Arabidopsis. Genetics 152: 401–412.
Weymann, K., Hunt, M., Uknes, S., Neuenschwander, U., Lawton, K., Steiner, H.Y. and Ryals, J. 1995. Suppression and restoration of lesion formation in Arabidopsis lsd mutants. Plant Cell 7: 2013–2022.
Whitham, S., Dinesh-Kumar, S.P., Choi, D., Hehl, R., Corr, C. and Baker, B. 1994. The product of the tobacco mosaic virus resistance gene N: similarity to Toll and the interleukin-1 receptor. Cell 78: 1011–1115.
Wolter, M., Hollricher, K., Salamini, F. and Schulze-Lefert, P. 1993. The mlo resistance alleles to powdery mildew infection in barley trigger a developmentally controlled defence mimic phenotype. Mol. Gen. Genet. 239: 122–128.
Yu, I.C., Parker, J. and Bent, A.F. 1998. Gene-for-gene disease resistance without the hypersensitive response in Arabidopsis dnd1 mutant. Proc. Natl. Acad. Sci. USA 95: 7819–7824.
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Shirasu, K., Schulze-Lefert, P. Regulators of cell death in disease resistance. Plant Mol Biol 44, 371–385 (2000). https://doi.org/10.1023/A:1026552827716
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DOI: https://doi.org/10.1023/A:1026552827716