Some pattern recognition receptors (PRRs) in plants, such as PEPRs, sense endogenous, damage‐associated molecular patterns (DAMPs) that are released during pathogen infection. In this issue of The EMBO Journal, Yamada and colleagues show that genetic or pathogen‐induced depletion of Arabidopsis BAK1, a co‐receptor for multiple PRRs, primes immune activation through PEPRs. The work illustrates a link between pathogen‐induced perturbation of BAK1 and DAMP signaling.
See also: K Yamada et al
Plants and animals employ immune receptors to defend against pathogens by sensing the presence of non‐self or altered‐self patterns. In both plants and animals, membrane‐localized pattern recognition receptors (PRRs) that recognize conserved microbe‐associated molecular patterns (MAMPs) mediate the first line of defense, pattern‐triggered immunity (PTI). In plants, BAK1 serves as a co‐receptor for multiple PRRs and plays critical roles in PTI. For instance, BAK1 associates with the PRR FLS2, acting as a co‐receptor to perceive bacterial flagellin upon infection (Macho & Zipfel, 2014). Given the importance of PRRs, it is not surprising that multiple pathogen effectors target PRR complexes to promote parasitism (Macho & Zipfel, 2015). Interestingly, the bak1 knockout (bak1‐ko) mutant displays hypersensitive response (HR)‐like cell death and enhanced resistance to biotrophic pathogens (Kemmerling et al, 2007). Mutation in BKK1, the closest homolog of BAK1, further enhances this resistance. Overexpression of full‐length or a truncated version of BAK1 also leads to similar autoimmune phenotypes (Domínguez‐Ferreras et al, 2015). HR‐like cell death in plants and inflammatory cell death in animals have very similar morphological features (Coll et al, 2011), although the role of HR‐like cell death in innate immunity is not well defined. Together, the existing evidence support that plants are able to sense the perturbation of BAK1 to activate immunity, but the downstream immune pathway remains unknown.
In addition to MAMPs, host‐derived damage‐associated molecular patterns (DAMPs) that are released during infection are also perceived by PRRs to activate PTI in plants. For instance, Arabidopsis Pep epitopes derived from pro‐peptides (PROPEPs) are perceived by a pair of close‐related receptors PEPR1 and PEPR2 (Huffaker et al, 2006; Yamaguchi et al, 2010). Oligogalacturonides (OGs) released from plant cell wall during pathogen infection are perceived by WAK1 (Brutus et al, 2010). Activation of PEPRs and WAK1 leads to immune outputs similar to those induced by MAMPs. While OGs are released by cell wall‐degrading enzymes produced by pathogens, whether the PEPR signaling is linked to specific perturbation in the host plant remains unclear. Thus, how pathogen infection leads to the activation of PEPR‐mediated immunity is not known.
In this issue of The EMBO Journal, Yamada et al (2015) investigate the molecular link between PEPR signaling and BAK1 perturbation, initially by studying the role of BAK1 in PEPR signaling. Surprisingly, genetic analyses showed that PEPR‐mediated signaling is sensitized instead of compromised in bak1‐ko mutants. The sensitization includes an increased responsiveness to peps, transcription of ProPeps, and release of ProPep proteins into the culture medium in response to Pep treatment. Further analyses demonstrated that the sensitized PEPR signaling largely accounts for the elevated disease resistance and cell death phenotypes in bak1‐ko mutants and bak1 bkk1 double mutant. BIK1 and PBL1, two cytoplasmic kinases previously shown to be required for PEPR signaling (Liu et al, 2013), also contribute to the autoimmune phenotype in bak1‐ko plants. The results demonstrate that depletion of BAK1 and its homolog BKK1 is linked to PEPR‐mediated DAMP signaling.
The sensitized PEPR signaling in BAK1‐depleted plants is at odds with the fact that BAK1 is a co‐receptor for PEPRs. One possible explanation for this is that other SERK members, which are close homologs of BAK1, can compensate for the absence of BAK1 in PEPR signaling. This notion was consistent with the authors' observation that PEPRs associate with four tested SERK members in response to Pep2. This differs from FLS2 signaling, as FLS2 preferentially associates with BAK1 in response to flagellin.
Are these findings biologically relevant? Yamada et al (2015) investigated the role of PEPR signaling in pathogen resistance in the presence or absence of BAK1. They found that PEPR signaling plays a critical role in basal defenses in the bak1 mutant, as the pepr1 pepr2 bak1 triple mutant displays enhanced susceptibility to virulent bacterial and oomycete pathogens. To investigate the biological relevance of BAK1 depletion and pathogen infection, Yamada et al (2015) assessed whether pathogen infection affected BAK1 accumulation. They found that BAK1 accumulation was not affected by infection with virulent or avirulent Pseudomonas syringae tomato (Pst) bacteria, but was significantly reduced during Colletotrichum higginsianum (Ch) infection. Importantly, pepr1 pepr2 plants showed enhanced susceptibility to Ch, a finding that is consistent with the notion that host plants sense perturbation of BAK1 upon Ch infection to sensitize PEPR signaling. Although Pst infection did not appear to alter the abundance of BAK1, it is formally possible that BAK1 is perturbed by some Pst effectors at the level of protein integrity or activity, which could result in the sensitization of PEPR signaling. Indeed, the Pst‐induced sensitization of PEPR signaling requires an intact type III secretion system that is essential for effector delivery. It will be important to test in the future if any pathogen effectors targeting BAK1 lead to PEPR sensitization.
One very interesting finding described by Yamada et al (2015) is that Pep and Pst induce the release of ProPep proteins into the extracellular space. The release of ProPeps in plants in response to pathogen infection is analogous to the release of inflammatory cytokines in animals in response to pathogen infection (Fig 1). How ProPeps are released and processed in plants remain to be examined. Another important unanswered question is how plants sense the perturbation of BAK1. The spontaneous cell death and enhanced resistance displayed by bak1‐ko plants is reminiscent of some lesion mimic mutants that develop autoimmunity caused by activation of intracellular NOD‐like receptors (NLRs), which often detect pathogen effectors indirectly by associating with effector targets (Cui et al, 2015). It remains to be determined whether any R proteins functionally associate with BAK1 to monitor its status. In this scenario, the undefined NLR‐mediated immunity is activated when BAK1 is perturbed by mutations or pathogen effectors. If this is the case, the next immediate question is whether the activation of NLR‐mediated immunity leads to sensitization of PEPR signaling or another DAMP pathway. Answers to these questions will shed new light on the plant immune system.
The work was supported by grants from Chinese Ministry of Science and Technology (Grant No. 2015CB910201) to J.M.Z. and National Science Fund for Distinguished Young Scholars of China (31525019) to D.T.
FundingChinese Ministry of Science and Technology2015CB910201
- © 2015 The Authors