Non-steroidal anti-inflammatory drugs target TWISTED DWARF1-regulated actin dynamics and auxin transport-mediated plant development

Tan S, Di Donato M, Glanc M, Zhang X, Klíma P, Liu J, Bailly A, Ferro N, Petrášek J, Geisler M, Friml J. 2020. Non-steroidal anti-inflammatory drugs target TWISTED DWARF1-regulated actin dynamics and auxin transport-mediated plant development. Cell Reports. 33(9), 108463.

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Author
Tan, ShutangIST Austria ; Di Donato, Martin; Glanc, MatoušIST Austria ; Zhang, XixiIST Austria ; Klíma, Petr; Liu, Jie; Bailly, Aurélien; Ferro, Noel; Petrášek, Jan; Geisler, Markus; Friml, JiríIST Austria
Department
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.
Publishing Year
Date Published
2020-12-01
Journal Title
Cell Reports
Acknowledgement
We thank Drs. Sebastian Bednarek (University of Wisconsin-Madison), Niko Geldner (University of Lausanne), and Karin Schumacher (Heidelberg University) for kindly sharing published Arabidopsis lines; Dr. Satoshi Naramoto for the pPIN2::PIN2-GFP; pVHA-a1::VHA-a1-mRFP reporter; the staff at the Life Science Facility and Bioimaging Facility, Monika Hrtyan, and Dorota Jaworska at IST Austria for technical support; and Drs. Su Tang (Texas A&M University), Melinda Abas (BOKU), Eva Benkova´ (IST Austria), Christian Luschnig (BOKU), Bartel Vanholme (Gent University), and the Friml group for valuable discussions. The research leading to these findings was funded by the European Union’s Horizon 2020 program (ERC grant agreement no. 742985, to J.F.), the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement no. 291734, the Swiss National Funds (31003A_165877, to M.G.), the Ministry of Education, Youth, and Sports of the Czech Republic (project no. CZ.02.1.01/0.0/0.0/16_019/0000738, EU Operational Programme ‘‘Research, development and education and Centre for Plant Experimental Biology’’), and the EU Operational Programme Prague - Competitiveness (project no. CZ.2.16/3.1.00/21519). S.T. was funded by a European Molecular Biology Organization (EMBO) long-term postdoctoral fellowship (ALTF 723-2015). X.Z. was partly supported by a PhD scholarship from the China Scholarship Council.
Volume
33
Issue
9
Article Number
108463
eISSN
IST-REx-ID

Cite this

Tan S, Di Donato M, Glanc M, et al. Non-steroidal anti-inflammatory drugs target TWISTED DWARF1-regulated actin dynamics and auxin transport-mediated plant development. Cell Reports. 2020;33(9). doi:10.1016/j.celrep.2020.108463
Tan, S., Di Donato, M., Glanc, M., Zhang, X., Klíma, P., Liu, J., … Friml, J. (2020). Non-steroidal anti-inflammatory drugs target TWISTED DWARF1-regulated actin dynamics and auxin transport-mediated plant development. Cell Reports. Elsevier. https://doi.org/10.1016/j.celrep.2020.108463
Tan, Shutang, Martin Di Donato, Matous Glanc, Xixi Zhang, Petr Klíma, Jie Liu, Aurélien Bailly, et al. “Non-Steroidal Anti-Inflammatory Drugs Target TWISTED DWARF1-Regulated Actin Dynamics and Auxin Transport-Mediated Plant Development.” Cell Reports. Elsevier, 2020. https://doi.org/10.1016/j.celrep.2020.108463.
S. Tan et al., “Non-steroidal anti-inflammatory drugs target TWISTED DWARF1-regulated actin dynamics and auxin transport-mediated plant development,” Cell Reports, vol. 33, no. 9. Elsevier, 2020.
Tan S, Di Donato M, Glanc M, Zhang X, Klíma P, Liu J, Bailly A, Ferro N, Petrášek J, Geisler M, Friml J. 2020. Non-steroidal anti-inflammatory drugs target TWISTED DWARF1-regulated actin dynamics and auxin transport-mediated plant development. Cell Reports. 33(9), 108463.
Tan, Shutang, et al. “Non-Steroidal Anti-Inflammatory Drugs Target TWISTED DWARF1-Regulated Actin Dynamics and Auxin Transport-Mediated Plant Development.” Cell Reports, vol. 33, no. 9, 108463, Elsevier, 2020, doi:10.1016/j.celrep.2020.108463.
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