16.05.2017

Molecular patterns on the surfaces of bacteria, viruses and fungi can trigger the plant's immune response. The corresponding receptors on the plant cell surface (Pattern Recognition Receptors, PRRs) recognize these patterns and forward the signal of an attacking pathogen into the plant cell interior. In the nucleus, the signaling cascade results in activation of genes, that provide the proteins necessary for defense.

Once triggered, the defense response also requires a mechanism that turns it off again. Often, negative feedback mechanisms mediate such a dampening of a process stimulated earlier. This is also the case for the plant immune response, as Marco Trujillo and colleagues recently demonstrated (Furlan et al. Changes in PUB22 ubiquitination modes triggered by MITOGEN-ACTIVATED PROTEIN KINASE3 dampen the immune response, Plant Cell, 2017; DOI: 10.1105/tpc.16.00654). They focus their research on ubiquitin-mediated protein degradation in the plant immune response. Crucial to this process is a Plant U-box 22 (PUB22) ubiquitin ligase. When a pathogen stimulates a PRR, PUB22 marks a specific target protein for degradation by attaching ubiquitins to it. Interestingly, plants without PUB22 are more resistant against pathogens, and thus, PUB22 with its ubiquitinating activity must be a negative regulator of the immune response. Accordingly, PUB22 has been a candidate mediator of negative feedback regulation.

A successful IPB-internal collaboration by Trujillo's lab, the lab of Justin Lee (Group Cellular Signaling) and the Proteome Analytics platform led by Wolfgang Hoehenwarter teamed up with japanese collaborators to elucidate the details of negative feedback mechanism in plant defense. In the absence of pathogen signals, Furlan et al. found that PUB22 dimerizes. The subunits of a PUB22 dimer ubiquitinate each other and are subsequently degraded. Therefore, under normal conditions, the negative immune regulator PUB22 is unstable. It will only become stable, when a pathogen signal is transduced from a PRR into the cell. It has been known that this signal transduction is realized via a phosphorylation cascade. That means, one phosphorylating enzyme, a so-called kinase, activates the next and thereby the signal proceeds until at the end, transcription factors are activated for the transcription of immune response genes. With their experiments, the researchers demonstrated that one of these kinases can also interact with and phosphorylate PUB22. Using mass spectrometry, they were able to identify the precise phosphorylation sites in PUB22, and so elucidate the effect of this modification. These phosphorylations hinder the dimerization and thus autoubiquitination of PUB22. Consequently, phosphorylated PUB22 does no longer mark itself but its target protein for degradation and thereby exerts its dampening effect on the defense response. The phosporylation cascade, that translates the pathogen signal into a defense response, at the same time triggers a process that inhibits this response. To understand the complex defense responses in plants is challenging but rewarding, as insights from this kind of basic research kann help in future development of robust crop plants.