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Non-steroidal Anti-inflammatory Drugs Target TWISTED DWARF1-Regulated Actin Dynamics and Auxin Transport-Mediated Plant Development.

Institute of Science and Technology Austria (IST Austria), Am Campus 1, 3400 Klosterneuburg, Austria. Department of Biology, University of Fribourg, 1700 Fribourg, Switzerland. Institute of Science and Technology Austria (IST Austria), Am Campus 1, 3400 Klosterneuburg, Austria; Department of Experimental Plant Biology, Faculty of Science, Charles University, Viničná 5, 128 43 Prague 2, Czech Republic. Institute of Science and Technology Austria (IST Austria), Am Campus 1, 3400 Klosterneuburg, Austria; Department of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences (BOKU), Muthgasse 18, 1190 Vienna, Austria. The Czech Academy of Sciences, Institute of Experimental Botany, Rozvojová 263, 165 02 Prague 6, Czech Republic. Department of Plant and Microbial Biology, University of Zurich, 8008 Zurich, Switzerland. University of Bonn, Mulliken Center for Theoretical Chemistry, Institute for Physical and Theoretical Chemistry, 53115 Bonn, Germany. Department of Experimental Plant Biology, Faculty of Science, Charles University, Viničná 5, 128 43 Prague 2, Czech Republic; The Czech Academy of Sciences, Institute of Experimental Botany, Rozvojová 263, 165 02 Prague 6, Czech Republic. Institute of Science and Technology Austria (IST Austria), Am Campus 1, 3400 Klosterneuburg, Austria. Electronic address: jiri.friml@ist.ac.at.

Cell reports. 2020;(9):108463
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Abstract

The widely used non-steroidal anti-inflammatory drugs (NSAIDs) are derivatives of the phytohormone salicylic acid (SA). SA is well known to regulate plant immunity and development, whereas there have been few reports focusing on the effects of NSAIDs in plants. Our studies here reveal that NSAIDs exhibit largely overlapping physiological activities to SA in the model plant Arabidopsis. NSAID treatments lead to shorter and agravitropic primary roots and inhibited lateral root organogenesis. Notably, in addition to the SA-like action, which in roots involves binding to the protein phosphatase 2A (PP2A), NSAIDs also exhibit PP2A-independent effects. Cell biological and biochemical analyses reveal that many NSAIDs bind directly to and inhibit the chaperone activity of TWISTED DWARF1, thereby regulating actin cytoskeleton dynamics and subsequent endosomal trafficking. Our findings uncover an unexpected bioactivity of human pharmaceuticals in plants and provide insights into the molecular mechanism underlying the cellular action of this class of anti-inflammatory compounds.