Salicylic acid in plant immunity and beyond

Abstract

As the most widely used herbal medicine in human history and a major defence hormone in plants against a broad spectrum of pathogens and abiotic stresses, salicylic acid (SA) has attracted major research interest. With applications of modern technologies over the past 30 years, studies of the effects of SA on plant growth, development, and defence have revealed many new research frontiers and continue to deliver surprises. In this review, we provide an update on recent advances in our understanding of SA metabolism, perception, and signal transduction mechanisms in plant immunity. An overarching theme emerges that SA executes its many functions through intricate regulation at multiple steps: SA biosynthesis is regulated both locally and systemically, while its perception occurs through multiple cellular targets, including metabolic enzymes, redox regulators, transcription cofactors, and, most recently, an RNA-binding protein. Moreover, SA orchestrates a complex series of post-translational modifications of downstream signaling components and promotes the formation of biomolecular condensates that function as cellular signalling hubs. SA also impacts wider cellular functions through crosstalk with other plant hormones. Looking into the future, we propose new areas for exploration of SA functions, which will undoubtedly uncover more surprises for many years to come.

Figure 1.

NPR1 is regulated by multiple E3 ubiquitin ligases. Under steady-state conditions, NPR1 is targeted for degradation by a CRL3^NPR4 ubiquitin ligase to avoid untimely activation of immunity. At the early onset of immunity, SA begins to accumulate and binds to NPR4, which prevents this protein from interacting with NPR1 (top left). This allows NPR1 to activate gene expression and promote cell survival during SAR (top right). Activation of ETI leads to much higher levels of SA, which promote recruitment of NPR1 to a CRL3^NPR3 ubiquitin ligase that targets NPR1 for degradation, thereby permitting cell death to occur (bottom left). Alternatively, the transcriptionally competent state of NPR1 in SAR can be deactivated by the SCF^HOS15 ubiquitin ligase (bottom right). Created with BioRender.com.

Figure 2.

Diverse PTMs dynamically regulate NPR1 localization and activities. In resting cells, NPR1 resides in the cytoplasm as a disulfide-linked (S-S) oligomer. Activation of immunity leads to the TRXh3- and TRXh5-mediated reduction of NPR1 oligomers and nuclear translocation of NPR1 promoted by SnRK2.8-mediated phosphorylation. Moreover, dephosphorylation of NPR1 at Ser55/59 and its SUMOylation both stimulate localization of NPR1 to the nuclear condensate (nSINC). SUMOylation also promotes NPR1's association with TGA transcription factors and is a prerequisite for phosphorylation (P) at Ser11/15, which stimulates NPR1's transcriptional activity by recruiting a CRL3 ligase that (mono)ubiquitinates NPR1. Sumo (S) and/or ubiquitin (Ub) may act as a molecular chaperone for SA binding, leading to a transcriptionally active NPR1-TGA complex. Eventually, ubiquitin chain elongation by an UBE4 ligase inactivates NPR1 and targets it to the proteasome. At the proteasome UPL3/4 ligases further decorate NPR1 with ubiquitin, which prevents its stalling during degradation and promotes proteasome processivity. NPR1 can be rescued from degradation and returned to its transcriptionally active state by the activities of proteasome-associated UBP6/7 deubiquitinases. In addition to its nuclear function, high SA levels, as found in tissues surrounding ETI-induced cell death, lead NPR1 to form cytoplasmic condensates (cSINCs), where it serves as a CRL3^NPR1 ligase that targets various cell death-inducing immune regulators for degradation to promote cell survival. Created with BioRender.com.

Figure 3.

NPR proteins mediate crosstalk between SA and other hormones. While NPR1 is essential for activation of SA-responsive genes during SAR (top center), it can also function as a potent inhibitor of JA-, GA-, and possibly auxin-responsive gene expression. NPR1 inhibits JA-responsive gene expression either by degrading ORA59 activators as part of a CRL3^NPR1 ligase (bottom right) or by blocking MYC activators' access to Mediator components (MED25) and associated RNA Polymerase II (RNAPII) complex (bottom center). In contrast to NPR1, both NPR3 and NPR4 activate JA-responsive genes during ETI by serving as a CRL3^NPR3/4 ligase to degrade the JA repressors JAZ and NPR1 (bottom left). Auxin-responsive genes are also inhibited by SA, but whether this process is dependent on NPR1 remains unknown (top left). Lastly, a probable CRL3^NPR1 ligase inhibits GA signaling by targeting the GA receptor GID1 for degradation, which blocks the removal of DELLA suppressors from GA-responsive genes (top right). Created with BioRender.com.