NSAIDs Target TWISTED DWARF1-Regulated Actin Dynamics and Auxin Transport-Mediated Plant Development
61 Pages Posted: 19 Jun 2020 Publication Status: Review CompleteMore...
The widely used non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin and ibuprofen, are derivatives of the phytohormone salicylic acid (SA). In plants, SA is well-known to regulate immunity as well as development, whereas there was no study focusing on the effects and mechanism of action of NSAIDs in plants. Our studies here in the model plant Arabidopsis thaliana reveal that NSAIDs exhibit largely overlapping physiological activities to SA. NSAID treatments in Arabidopsis seedlings 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 exhibit also PP2A-independent effects. Cell biological and biochemical analyses unravel that many NSAIDs bind directly to and inhibit the chaperone activity of the FKBP42, TWISTED DWARF1, thereby regulating the dynamics of actin cytoskeleton and subsequent endosomal trafficking. Our findings uncover an unexpected bioactivity of human pharmaceuticals in plants, and provide novel insights into the molecular mechanism underlying the cellular action of this class of anti-inflammatory compounds.
Keywords: Arabidopsis, auxin, auxin transport inhibitor, ATI, endocytosis, endosome, endosomal trafficking, endocytic trafficking, polar auxin transport, PAT, non-steroidal anti-inflammatory drug, NSAID, FKBP
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