Chemical screen identifies a small molecule antagonizing JA-Ile perception and auxin responses

The phytohormone JA-Ile regulates many stress responses and developmental processes in plants. A co-receptor complex formed by the F-box protein COI1 and a JAZ repressor perceives the hormone. JA-Ile antagonists are invaluable tools to explore the role of JA-Ile in specific tissues and developmental stages, and to identify novel regulatory processes of the signalling pathway. Using two complementary chemical screens we identified three compounds exhibiting a robust inhibitory effect on both the hormone-mediated COI-JAZ interaction and degradation of JAZ1 and JAZ9 in vivo. One molecule, J4, also restrains specific JA-induced physiological responses in planta, such as JA-mediated gene expression, growth inhibition, chlorophyll degradation and anthocyanin accumulation. Interaction experiments with purified proteins indicate that J4 directly interferes with the formation of the Arabidopsis thaliana COI1-JAZ complex induced by the hormone. The antagonistic effect of J4 on COI1-JAZ also occurs in the liverwort Marchantia polymorpha, suggesting the conservation of its mode of action in land plants. Besides JA signalling, this molecule works as an antagonist of the closely-related auxin signalling pathway, preventing TIR1/Aux-IAA interaction, and auxin responses in planta such as hormone-mediated degradation of an auxin repressor, gene expression and gravitropic response. However, J4 does not affect other hormonal pathways. Altogether, our results show that this dual antagonist competes with JA-Ile and auxin preventing the formation of phylogenetically related receptor complexes. J4 may represent a useful tool to dissect both the JA-Ile and auxin pathways in particular tissues and developmental stages in a reversible way.