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A chemical inhibitor of jasmonate signaling targets JAR1 in Arabidopsis thaliana

Nature Chemical Biology volume 10, pages 830–836 (2014)Cite this article

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Abstract

Jasmonates are lipid-derived plant hormones that regulate plant defenses and numerous developmental processes. Although the biosynthesis and molecular function of the most active form of the hormone, (+)-7-iso-jasmonoyl-L-isoleucine (JA-Ile), have been unraveled, it remains poorly understood how the diversity of bioactive jasmonates regulates such a multitude of plant responses. Bioactive analogs have been used as chemical tools to interrogate the diverse and dynamic processes of jasmonate action. By contrast, small molecules impairing jasmonate functions are currently unknown. Here, we report on jarin-1 as what is to our knowledge the first small-molecule inhibitor of jasmonate responses that was identified in a chemical screen using Arabidopsis thaliana. Jarin-1 impairs the activity of JA-Ile synthetase, thereby preventing the synthesis of the active hormone, JA-Ile, whereas closely related enzymes are not affected. Thus, jarin-1 may serve as a useful chemical tool in search for missing regulatory components and further dissection of the complex jasmonate signaling networks.

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Figure 1: Identification and characterization of jarin-1.
Figure 2: Jarin-1 inhibits degradation of the transcriptional repressor protein JAZ1 initiated by JAMe treatment.
Figure 3: Jarin-1 selectively inhibits enzymatic activity of JAR1.
Figure 4: Jarin-1 inhibits production of JA-Ile in Arabidopsis leaves.

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Acknowledgements

We thank I. Somssich, C. Wasternack and members of our labs for critical reading of the manuscript and stimulating discussions. We also thank R. Solano (Universidad Autónoma, Madrid, Spain) for kindly providing seeds of the transgenic plant expressing CaMV35S∷JAZ1-GUS and J. Mundy (University of Copenhagen, Denmark) for seeds of plants harboring the dual reporter system LOX2p∷LUC/LOX2p∷GUS. This work was supported by the Max Planck Society (to E.K.), the Deutsche Forschungsgemeinschaft (DFG, Ko1192/6-1/2/3 to E.K.) and a European Research Council Starting grant (grant no. 258413 to M.K.). C.M. was the recipient of an International Max Planck Research School doctoral fellowship (Max Planck Institute for Plant Breeding Research, Köln). Additional support was provided by the National Science Foundation (MCB-1157771 to J.M.J.) and the United States Department of Agriculture–National Institute of Food and Agriculture Predoctoral Fellowship Program (MOW-2010-05240 to C.S.W.).

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Authors and Affiliations

  1. Chemical Biology Laboratory, Max Planck Institute for Plant Breeding Research, Köln, Germany

    Christian Meesters & Erich Kombrink

  2. Department of Chemical Biology, Center for Medical Biotechnology, Faculty of Biology, University Duisburg-Essen, Essen, Germany

    Christian Meesters, Timon Mönig, Julian Oeljeklaus, Daniel Krahn & Markus Kaiser

  3. Department of Biology, Washington University, St. Louis, Missouri, USA

    Corey S Westfall & Joseph M Jez

  4. Department of Cell and Metabolic Biology, Leibniz Institute of Plant Biochemistry, Halle (Saale), Germany

    Bettina Hause

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  1. Christian Meesters
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Contributions

C.M. performed the chemical screens and all of the biochemical (chemical biology) work leading to target identification, including enzyme kinetics of JAR1. T.M. and J.O. synthesized jarin-1, JA-Ile and other derivatives; D.K. performed proteasome assays; C.S.W. and J.M.J. performed enzyme activity assays and crystallographic and docking studies; B.H. determined jasmonate levels; E.K., M.K., C.M. and J.M.J. conceived experiments, analyzed data and wrote the manuscript.

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Correspondence to Markus Kaiser or Erich Kombrink.

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Meesters, C., Mönig, T., Oeljeklaus, J. et al. A chemical inhibitor of jasmonate signaling targets JAR1 in Arabidopsis thaliana. Nat Chem Biol 10, 830–836 (2014). https://doi.org/10.1038/nchembio.1591

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