A new chemical tool to analyze plant hormone pathways is established by Prof. Dr. Markus Kaiser, Centre for Medical Biotechnology, University of Duisburg-Essen (UDE), and Dr. Erich Kombrink, Max Planck Institute for Plant Breeding Research, Cologne. In the latest issue of „Nature Chemical Biology“, the researchers disclose a small molecule inhibitor, which interferes with the activity of the plant hormone jasmonic acid. The approach resembles concepts, which are well established in medical therapy and opens new opportunities for plant research. (Doi:10.1038/nchembio.1591).
Currently, research into plant hormone signalling relies primarily on molecular genetics. Genes of interest are modified or extinguished to then study resultant changes in the plant’s phenotype. This strategy is powerful but has its limitations, as is highlighted by the plant hormone jasmonic acid.
Although jasmonic acid controls a diversity of biological functions, as flower formation, root growth, protection against insect attack and infections, wound healing, plant aging and others, only one signal transduction pathway has been elucidated so far.
This single pathway however is not sufficient to explain the broad spectrum of hormone actions. Other, so far unknown, signaling pathways and mechanisms must exist. To get a better understanding of jasmonic acid’s signaling mechanisms, alternative experimental approaches are therefore required. The teams from Essen and Cologne took up this challenge and used a procedure, which is well established in medical research but still rarely used in plant science:
They searched for a chemical drug that can be used to block a specific signalling pathway. In medicine, such compounds find applications as drugs to treat diseases. In plant science, however, such inhibitors may represent important chemical tools to advance the study of plant signalling pathways.
In the search of candidate inhibitors of jasmonic acid signalling, the scientists performed studies in intact plants. They started with a screening in the ‘model plant’ Arabidopsis thaliana. From 1.728 tested compounds, 16 molecules were identified that impaired jasmonic acid signalling. These were then studied in more detail and finally, only one compound was confirmed as a suitable specific inhibitor.
The compound was called Jarin-1. “Structurally, the compound is a plant alkaloid whose amino groups may carry different side chains” the researchers comment. “The activity of the compound depends on a specific side chain. Modifications deactivate the inhibitor. As a final proof of the active chemical structure, we synthesized it from scratch.’
As a next step the scientists looked for the molecular target of the new inhibitor. The already known signal transduction pathway of jasmonic acid starts with an enzyme called JAR1 that links the plant hormone jasmonic acid to the amino acid isoleucine. The resulting chemical product then modulates the transcription of various genes that together form the particular biological activity of jasmonic acid.
Kombrink and Kaiser were able to show that this enzyme JAR1 is the target of the inhibitor Jarin-1. Inhibition of JAR1 causes depletion of the required jasmonic acid-isoleucine conjugate, thus impairing gene transcription. They furthermore found that the molecule Jarin-1 is not only active in Arabidopsis but also in Candamine hirsuta, lamb’s cress. Therefore, the inhibitor seems to be broadly applicable and thus may be used in future applications to advance the understanding of jasmonic acid signalling.
What is particular about this new approach and caused the renowned journal “Nature Chemical Biology” to publish the work? Small molecules are promising new tools for plant research. The scientists demonstrate exemplarily how to screen for a specific small molecule inhibitor, how to characterize it and how to identify its target protein and they point out possible applications. The scope of the study turns the publication into something highly special.
Dr. Erich Kombrink
Max-Planck-Institut for Plant Breeding Research
Telefon: +49 221 5062 320
Prof. Dr. Markus Kaiser
Center for Medical Biotechnology
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