Plant immunology: A life or death switch

Journal name:
Nature
Volume:
486,
Pages:
198–199
Date published:
DOI:
doi:10.1038/486198a
Published online

The identification of two receptors for salicylic acid reveals how the hormone controls cell death and survival during plant immune responses, in tissues close to and distant from the site of infection. See Letter p.228

Immunity to microbial infection is an inherent feature of multicellular organisms. In plants, immune responses are activated when cellular receptors recognize microbial proteins (effectors) that betray the invader to the plant's surveillance system1, 2. This activation requires the plant hormone salicylic acid, which is produced on microbial attack3. But how plants detect the hormone, and how it performs its immunity-associated functions, has remained unclear. On page 228 of this issue, Fu et al.4 report the identification of two salicylic acid receptors in the model plant Arabidopsis thaliana, and provide a fascinating explanation of how the hormone controls both cell death at the site of infection, and cell survival and immune activation in non-infected tissues.

In plants, effector-triggered immunity (ETI) is often accompanied by programmed cell death (PCD) at the infection site. In addition to participating in local immune responses, PCD triggers long-lasting immunity against a broad spectrum of microbes throughout the plant — a protective mechanism referred to as systemic acquired resistance3. Salicylic acid participates in these immune responses by controlling the movement of a protein called NPR1 (non-expresser of pathogenesis-related genes 1) from the cell cytoplasm to the nucleus5. Once in the nucleus, NPR1 regulates the expression of plant defence genes. Because mutant plants that are insensitive to salicylic acid and plants that lack NPR1 exhibit similar immune defects, NPR1 was previously proposed6 to be a salicylic acid receptor. However, Fu et al.4 did not detect any physical interaction between salicylic acid and NPR1, suggesting that NPR1 does not serve this receptor function.

What, then, could be the bona fide salicylic acid receptor mediating local and systemic immune activation in plants? The research group presenting the current paper has previously shown7 that the proper functioning of NPR1 requires that the protein is broken down by cellular protein-degradation machinery called the proteasome. So Fu and colleagues hypothesized that adaptor proteins that link NPR1 to the proteasome might be receptors for salicylic acid. Two members of the NPR protein family, NPR3 and NPR4, exhibit a protein-domain structure that is characteristic of such adaptor proteins, leading the authors to surmise that these proteins could be the proteasome adaptors that mediate NPR1 degradation. To validate this assumption, the researchers demonstrated that NPR1 is degraded by the proteasome in wild-type A. thaliana plants, but not in plants in which the genes for NPR3 and NPR4 have both been knocked out.

Fu and colleagues used in vitro protein–protein interaction studies to assess the effect of salicylic acid on the formation of protein complexes between NPR1 and NPR3 or NPR4. The authors found, surprisingly, that salicylic acid promotes NPR1–NPR3 interaction, but disrupts formation of the NPR1–NPR4 complex. Thus it seems that salicylic acid interacts physically with NPR3 and NPR4 in a receptor-like manner, but that this interaction has opposing effects on the adaptor proteins' interactions with NPR1. The authors also found that although NPR3 and NPR4 both bind to salicylic acid, NPR4 binds with greater affinity than does NPR3. Hence, Arabidopsis plants contain two salicylic acid receptors, NPR3 and NPR4, which differ in their affinity for the hormone and in their roles in NPR1 degradation, with NPR3 mediating NPR1 breakdown only in the presence of salicylic acid and NPR4 only in its absence.

What are the biological consequences of NPR3- or NPR4-mediated degradation of NPR1? Fu and colleagues found that both local PCD and local ETI responses to bacterial infection were compromised in plants lacking the genes encoding both NPR3 and NPR4. The impairment of PCD, combined with the fact that NPR1 accumulates in the mutant plants (because it cannot be degraded) suggests that NPR1 suppresses PCD in wild-type plants. Because salicylic acid levels are highest at infection sites8, Fu et al. propose that binding of the hormone to the lower-affinity receptor NPR3 mediates NPR1 degradation and de-repression of PCD and ETI in infected cells (Fig. 1).

Figure 1: Salicylic acid-mediated control of plant cell death and survival.
Salicylic acid-mediated control of plant cell death and survival.

On microbial infection, levels of the plant hormone salicylic acid increase, with its concentration decreasing gradually with increasing distance from the site of infection. Fu et al.4 show that at high salicylic acid concentrations — typically found in infected areas of the plant — the receptor NPR3, which binds salicylic acid with low affinity, mediates degradation of the cell-death suppressor NPR1 (left panel), thereby favouring programmed cell death and local effector-triggered immunity. However, at the lower salicylic acid concentrations typically found in cells distant from the infection site, salicylic acid cannot bind to the low-affinity receptor NPR3, so cell death is blocked. In these cells, salicylic acid instead binds to the high-affinity receptor NPR4 (right panel), blocking degradation of NPR1, and thereby favouring cell survival and the expression of genes associated with systemic immunity.

However, infection causes salicylic acid levels to increase systemically as well as locally, with its concentration decreasing gradually with increasing distance from the infection site8. In cells farther away from the infected area, salicylic acid levels are likely to drop below the concentration required for NPR3-mediated NPR1 degradation and, thus, PCD. Fu and colleagues propose that, in these cells, salicylic acid binds instead to the higher-affinity receptor NPR4, which inhibits NPR4-mediated NPR1 degradation and thereby facilitates NPR1 accumulation, cell survival and subsequent salicylic acid-dependent gene expression (Fig. 1). Consistent with this model, the authors showed that NPR1 levels are lowest in cells undergoing PCD and highest in cells surrounding PCD lesions.

Several mutant plants that exhibit runaway PCD have been identified9, and the question of how plants control PCD has been a major area of research. Fu and colleagues' findings provide compelling evidence that salicylic acid acts as an immune signal to determine cell fate in plant immunity. Studies investigating plant proteins associated with abnormal PCD should now examine whether these proteins might contribute to the functionality of NPR3 or NPR4.

Salicylic acid is the only major plant hormone for which the receptor has remained elusive. Fu and colleagues' demonstration that the two salicylic acid receptors control distinct defence strategies by de-repressing local cell death and immunity at the infection site in one case, and systemic immunity remote from the infection site in the other, is reminiscent of the de-repression of physiological programs enacted by other plant hormones, such as auxin, gibberellic acid and jasmonic acid10. However, NPR3 and NPR4 are the first plant-hormone sensors for which differences in binding affinity have been shown to mediate differential control of plant responses. Because most plant hormones regulate multiple aspects of plant life, it is certainly possible that other plant hormone receptors use a comparable mode of action. Consistent with this idea is the recent identification11 of auxin hormone-binding proteins that have different ligand affinities, suggesting that plants also have means for differential sensing of auxin1.

References

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  1. Andrea A. Gust and Thorsten Nürnberger are in the Centre of Plant Molecular Biology, Department of Plant Biochemistry, University of Tübingen, D-72076 Tübingen, Germany.

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