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


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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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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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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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).

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