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NPR3 and NPR4 are receptors for the immune signal salicylic acid in plants

Nature volume 486, pages 228–232 (2012)Cite this article

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Abstract

Salicylic acid (SA) is a plant immune signal produced after pathogen challenge to induce systemic acquired resistance. It is the only major plant hormone for which the receptor has not been firmly identified. Systemic acquired resistance in Arabidopsis requires the transcription cofactor nonexpresser of PR genes 1 (NPR1), the degradation of which acts as a molecular switch. Here we show that the NPR1 paralogues NPR3 and NPR4 are SA receptors that bind SA with different affinities. NPR3 and NPR4 function as adaptors of the Cullin 3 ubiquitin E3 ligase to mediate NPR1 degradation in an SA-regulated manner. Accordingly, the Arabidopsis npr3 npr4 double mutant accumulates higher levels of NPR1, and is insensitive to induction of systemic acquired resistance. Moreover, this mutant is defective in pathogen effector-triggered programmed cell death and immunity. Our study reveals the mechanism of SA perception in determining cell death and survival in response to pathogen challenge.

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Figure 1: NPR3 and NPR4 mediate degradation of NPR1.
Figure 2: SA directly regulates interactions between NPR proteins.
Figure 3: NPR3 and NPR4 bind SA.
Figure 4: SA receptors control NPR1 stability to regulate SAR and ETI.

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References

  1. Jones, J. D. & Dangl, J. L. The plant immune system. Nature 444, 323–329 (2006)

    Article  ADS  CAS  Google Scholar 

  2. Lorrain, S., Vailleau, F., Balague, C. & Roby, D. Lesion mimic mutants: keys for deciphering cell death and defense pathways in plants? Trends Plant Sci. 8, 263–271 (2003)

    Article  CAS  Google Scholar 

  3. Durrant, W. E. & Dong, X. Systemic acquired resistance. Annu. Rev. Phytopathol. 42, 185–209 (2004)

    Article  CAS  Google Scholar 

  4. Chen, Z., Silva, H. & Klessig, D. Involvement of reactive oxygen species in the induction of sytemic acquired resistance by salicylic acid in plants. Science 262, 1883–1886 (1993)

    Article  ADS  CAS  Google Scholar 

  5. Park, S. W., Kaimoyo, E., Kumar, D., Mosher, S. & Klessig, D. F. Methyl salicylate is a critical mobile signal for plant systemic acquired resistance. Science 318, 113–116 (2007)

    Article  ADS  CAS  Google Scholar 

  6. Slaymaker, D. H. et al. The tobacco salicylic acid-binding protein 3 (SABP3) is the chloroplast carbonic anhydrase, which exhibits antioxidant activity and plays a role in the hypersensitive defense response. Proc. Natl Acad. Sci. USA 99, 11640–11645 (2002)

    Article  ADS  CAS  Google Scholar 

  7. Cao, H., Glazebrook, J., Clark, J. D., Volko, S. & Dong, X. The Arabidopsis NPR1 gene that controls systemic acquired resistance encodes a novel protein containing ankyrin repeats. Cell 88, 57–63 (1997)

    Article  CAS  Google Scholar 

  8. Spoel, S. H. & Dong, X. How do plants achieve immunity? Defence without specialized immune cells. Nature Rev. Immunol. 12, 89–100 (2012)

    Article  CAS  Google Scholar 

  9. Pintard, L., Willems, A. & Peter, M. Cullin-based ubiquitin ligases: Cul3-BTB complexes join the family. EMBO J. 23, 1681–1687 (2004)

    Article  CAS  Google Scholar 

  10. Spoel, S. H. et al. Proteasome-mediated turnover of the transcription coactivator NPR1 plays dual roles in regulating plant immunity. Cell 137, 860–872 (2009)

    Article  CAS  Google Scholar 

  11. Zhang, Y. et al. Negative regulation of defense responses in Arabidopsis by two NPR1 paralogs. Plant J. 48, 647–656 (2006)

    Article  CAS  Google Scholar 

  12. Santner, A. & Estelle, M. Recent advances and emerging trends in plant hormone signalling. Nature 459, 1071–1078 (2009)

    Article  ADS  CAS  Google Scholar 

  13. Tan, X. et al. Mechanism of auxin perception by the TIR1 ubiquitin ligase. Nature 446, 640–645 (2007)

    Article  ADS  CAS  Google Scholar 

  14. Sheard, L. B. et al. Jasmonate perception by inositol-phosphate-potentiated COI1-JAZ co-receptor. Nature 468, 400–405 (2010)

    Article  ADS  CAS  Google Scholar 

  15. Métraux, J.-P. et al. in Advances in Molecular Genetics of Plant-Microbe Interactions Vol. 1 (eds Hennecke, H. & Verma, D. P. S. ) 432–439 (Kluwer Academic Publishers, 1991)

  16. Mou, Z., Fan, W. & Dong, X. Inducers of plant systemic acquired resistance regulate NPR1 function through redox changes. Cell 113, 935–944 (2003)

    Article  CAS  Google Scholar 

  17. Nawrath, C., Heck, S., Parinthawong, N. & Métraux, J.-P. 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 (2002)

    Article  CAS  Google Scholar 

  18. Wildermuth, M. C., Dewdney, J., Wu, G. & Ausubel, F. M. Isochorismate synthase is required to synthesize salicylic acid for plant defence. Nature 414, 562–565 (2001)

    Article  ADS  CAS  Google Scholar 

  19. Gaffney, T. et al. Requirement of salicylic acid for the induction of systemic acquired resistance. Science 261, 754–756 (1993)

    Article  ADS  CAS  Google Scholar 

  20. Malamy, J., Carr, J. P., Klessig, D. F. & Raskin, I. Salicylic acid: a likely endogenous signal in the resistance response of tobacco to viral infection. Science 250, 1002–1004 (1990)

    Article  ADS  CAS  Google Scholar 

  21. Enyedi, A. J., Yalpani, N., Silverman, P. & Raskin, I. Localization, conjugation, and function of salicylic acid in tobacco during the hypersensitive reaction to tobacco mosaic virus. Proc. Natl Acad. Sci. USA 89, 2480–2484 (1992)

    Article  ADS  CAS  Google Scholar 

  22. Dorey, S. et al. Spatial and temporal induction of cell death, defense genes, and accumulation of salicylic acid in tobacco leaves reacting hypersensitively to a fungal glycoprotein. Mol. Plant Microbe Interact. 10, 646–655 (1997)

    Article  CAS  Google Scholar 

  23. Torres, M. A., Jones, J. D. G. & Dangl, J. L. Pathogen-induced, NADPH oxidase-derived reactive oxygen intermediates suppress spread of cell death in Arabidopsis thaliana. Nature Genet. 37, 1130–1134 (2005)

    Article  CAS  Google Scholar 

  24. Lu, H. et al. Genetic analysis of acd6-1 reveals complex defense networks and leads to identification of novel defense genes in Arabidopsis. Plant J. 58, 401–412 (2009)

    Article  CAS  Google Scholar 

  25. Rate, D. N. & Greenberg, J. T. The Arabidopsis aberrant growth and death2 mutant shows resistance to Pseudomonas syringae and reveals a role for NPR1 in suppressing hypersensitive cell death. Plant J. 27, 203–211 (2001)

    Article  CAS  Google Scholar 

  26. Dieterle, M. et al. Molecular and functional characterization of Arabidopsis Cullin 3A. Plant J. 41, 386–399 (2005)

    Article  CAS  Google Scholar 

  27. Mackey, D., Holt, B. F., Wiig, A. & Dangl, J. L. RIN4 interacts with Pseudomonas syringae type III effector molecules and is required for RPM1-mediated resistance in Arabidopsis. Cell 108, 743–754 (2002)

    Article  CAS  Google Scholar 

  28. Rossignol, P., Collier, S., Bush, M., Shaw, P. & Doonan, J. H. Arabidopsis POT1A interacts with TERT-V(I8), an N-terminal splicing variant of telomerase. J. Cell Sci. 120, 3678–3687 (2007)

    Article  CAS  Google Scholar 

  29. Nallamsetty, S., Austin, B. P., Penrose, K. J. & Waugh, D. S. Gateway vectors for the production of combinatorially-tagged His6-MBP fusion proteins in the cytoplasm and periplasm of Escherichia coli. Protein Sci. 14, 2964–2971 (2005)

    Article  CAS  Google Scholar 

  30. Fan, W. & Dong, X. In vivo interaction between NPR1 and transcription factor TGA2 leads to salicylic acid-mediated gene activation in Arabidopsis. Plant Cell 14, 1377–1389 (2002)

    Article  CAS  Google Scholar 

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Acknowledgements

We thank Y. Zhang for sharing the npr3, npr4, npr3 npr4 and npr1 npr3 npr4 mutants; J. Song for providing the NPR3 and NPR4 Y2H constructs; Z. Mou for providing the data on the NPR1–GFP protein levels in the nahG transgenic plants, P. Zhou for discussion of the work and for critiquing the manuscript. This work was supported by the Hargitt Fellowship (to Z.Q.F.), grants GM069594-05 (to X.D.), CA107134 (to N.Z.), T32GM008268-23 (to J.R.), Grants-in-Aid for Scientific Research (no. 23120520) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (to Y.T). and the Royal Society Uf090321 (to S.H.S.). N.Z. is a Howard Hughes Medical Institute investigator and X.D. is a Howard Hughes Medical Institute-Gordon and Betty Moore Foundation investigator.

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Author notes

  1. Zheng Qing Fu, Shunping Yan and Abdelaty Saleh: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biology, Howard Hughes Medical Institute–Gordon and Betty Moore Foundation, PO Box 90338, Duke University, Durham, 27708, North Carolina, USA

    Zheng Qing Fu, Shunping Yan, Abdelaty Saleh, Wei Wang, Rajinikanth Mohan & Xinnian Dong

  2. Department of Pharmacology, Howard Hughes Medical Institute, University of Washington, PO Box 357280, Seattle, Washington 98195, USA,

    James Ruble & Ning Zheng

  3. Faculty of Agriculture, Kagawa University, Miki, Kagawa 761-0795, Japan,

    Nodoka Oka

  4. Institute of Molecular Plant Sciences, University of Edinburgh, Edinburgh EH9 3JR, UK,

    Steven H. Spoel

  5. Life Science Research Center, Institute of Research Promotion, Kagawa University, 2393 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0795, Japan,

    Yasuomi Tada

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Contributions

Z.Q.F., S.Y., A.S., R.M. and S.H.S. conceived and discovered that NPR3 and NPR4 mediate NPR1 degradation. Z.Q.F., A.S. and S.Y. found that SA regulates the interactions between the NPR proteins. S.Y., W.W. and A.S. found that NPR3 and NPR4 can bind SA with different affinities. J.R. and N.Z. showed that purified NPR4 recombinant protein exists as a tetramer, which is competent in SA binding. Z.Q.F., W.W. and R.M. demonstrated that the npr3 and npr4 single and double mutants are impaired in ETI and SAR. N.O. and Y.T. observed in situ accumulation of NPR1(C82A)–GFP in response to Psm ES4326/avrRpt2. S.H.S. provided data on the detection of NPR1–GFP protein in eds5 and ics1 plants. X.D. designed the research and, together with Z.F., S.Y., W.W., S.H.S., A.S. and R.M., wrote the manuscript.

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Correspondence to Xinnian Dong.

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The authors declare no competing financial interests.

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Fu, Z., Yan, S., Saleh, A. et al. NPR3 and NPR4 are receptors for the immune signal salicylic acid in plants. Nature 486, 228–232 (2012). https://doi.org/10.1038/nature11162

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