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NSAIDs Target TWISTED DWARF1-Regulated Actin Dynamics and Auxin Transport-Mediated Plant Development

61 Pages Posted: 19 Jun 2020 Publication Status: Review Complete

See all articles by Shutang Tan

Shutang Tan

Institute of Science and Technology (IST) Austria

Martin Di Donato

University of Fribourg - Department of Biology

Matouš Glanc

Institute of Science and Technology (IST) Austria

Xixi Zhang

Institute of Science and Technology (IST) Austria

Petr Klíma

Czech Academy of Sciences - Institute of Experimental Botany

Aurélien Bailly

University of Zurich - Department of Plant and Microbial Biology

Jan Petrášek

Charles University - Department of Experimental Plant Biology

Markus Geisler

University of Fribourg - Department of Biology

Jiri Friml

Institute of Science and Technology (IST) Austria

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Abstract

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

Suggested Citation

Tan, Shutang and Di Donato, Martin and Glanc, Matouš and Zhang, Xixi and Klíma, Petr and Bailly, Aurélien and Petrášek, Jan and Geisler, Markus and Friml, Jiri, NSAIDs Target TWISTED DWARF1-Regulated Actin Dynamics and Auxin Transport-Mediated Plant Development. Available at SSRN: https://ssrn.com/abstract=3613761 or http://dx.doi.org/10.2139/ssrn.3613761
This version of the paper has not been formally peer reviewed.

Shutang Tan

Institute of Science and Technology (IST) Austria ( email )

Klosterneuburg, 3400
Austria

Martin Di Donato

University of Fribourg - Department of Biology

Fribourg
Switzerland

Matouš Glanc

Institute of Science and Technology (IST) Austria

Klosterneuburg, 3400
Austria

Xixi Zhang

Institute of Science and Technology (IST) Austria

Klosterneuburg, 3400
Austria

Petr Klíma

Czech Academy of Sciences - Institute of Experimental Botany

Brno, CZ-60300
Czech Republic

Aurélien Bailly

University of Zurich - Department of Plant and Microbial Biology

Rämistrasse 71
Zürich, CH-8006
Switzerland

Jan Petrášek

Charles University - Department of Experimental Plant Biology

Celetná 13
Praha 1, 116 36
Czech Republic

Markus Geisler

University of Fribourg - Department of Biology

Fribourg
Switzerland

Jiri Friml (Contact Author)

Institute of Science and Technology (IST) Austria ( email )

Klosterneuburg, 3400
Austria

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