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.

Department of Biology University of Fribourg 1700 Fribourg Switzerland

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

Department of Plant and Microbial Biology University of Zurich 8008 Zurich Switzerland

Institute of Science and Technology Austria Am Campus 1 3400 Klosterneuburg Austria

Institute of Science and Technology 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 Muthgasse 18 1190 Vienna Austria

The Czech Academy of Sciences Institute of Experimental Botany Rozvojová 263 165 02 Prague 6 Czech Republic

University of Bonn Mulliken Center for Theoretical Chemistry Institute for Physical and Theoretical Chemistry 53115 Bonn Germany

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