Chemical inhibition of Arabidopsis PIN-FORMED auxin transporters by the anti-inflammatory drug naproxen

Xia, Jing; Kong, Mengjuan; Yang, Zhisen; Sun, Lianghanxiao; Peng, Yakun; Mao, Yanbo; Wei, Hong; Ying, Wei; Gao, Yongxiao; Friml, Jiří; Weng, Jianping; Liu, Xin; Sun, Linfeng; Tan, Shutang

Chemical inhibition of Arabidopsis PIN-FORMED auxin transporters by the anti-inflammatory drug naproxen

Xia J, Kong M, Yang Z, Sun L, Peng Y, Mao Y, Wei H, Ying W, Gao Y, Friml J, Weng J, Liu X, Sun L, Tan S. 2023. Chemical inhibition of Arabidopsis PIN-FORMED auxin transporters by the anti-inflammatory drug naproxen. Plant Communications. 4(6), 100632.

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DOI

10.1016/j.xplc.2023.100632

Journal Article | Published | English

Author

Xia, Jing; Kong, Mengjuan; Yang, Zhisen; Sun, Lianghanxiao; Peng, Yakun; Mao, Yanbo; Wei, Hong; Ying, Wei; Gao, Yongxiao; Friml, Jirí^ISTA ; Weng, Jianping; Liu, Xin
All

Department

Friml Group

Abstract

The phytohormone auxin plays central roles in many growth and developmental processes in plants. Development of chemical tools targeting the auxin pathway is useful for both plant biology and agriculture. Here we reveal that naproxen, a synthetic compound with anti-inflammatory activity in humans, acts as an auxin transport inhibitor targeting PIN-FORMED (PIN) transporters in plants. Physiological experiments indicate that exogenous naproxen treatment affects pleiotropic auxin-regulated developmental processes. Additional cellular and biochemical evidence indicates that naproxen suppresses auxin transport, specifically PIN-mediated auxin efflux. Moreover, biochemical and structural analyses confirm that naproxen binds directly to PIN1 protein via the same binding cavity as the indole-3-acetic acid substrate. Thus, by combining cellular, biochemical, and structural approaches, this study clearly establishes that naproxen is a PIN inhibitor and elucidates the underlying mechanisms. Further use of this compound may advance our understanding of the molecular mechanisms of PIN-mediated auxin transport and expand our toolkit in auxin biology and agriculture.

Publishing Year

2023

Date Published

2023-11-13

Journal Title

Plant Communications

Acknowledgement

This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB37020103 to Linfeng Sun); research funds from the Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Division of Life Sciences and Medicine, University of Science and Technology of China (QYPY20220012 to S.T.); start-up funding from the University of Science and Technology of China and the Chinese Academy of Sciences (GG9100007007, KY9100000026,KY9100000051, and KJ2070000079 to S.T.); the National Natural Science Foundation of China (31900885 to X.L. and 31870732 to Linfeng Sun); the Natural Science Foundation of Anhui Province (2008085MC90 to X.L. and 2008085J15 to Linfeng Sun); the Fundamental Research Funds for the Central Universities (WK9100000021 to S.T. and WK9100000031 to Linfeng Sun); and the USTC Research Funds of the Double First-Class Initiative (YD9100002016 to S.T. and YD9100002004 to Linfeng Sun). Linfeng Sun is supported by an Outstanding Young Scholar Award from the Qiu Shi Science and Technologies Foundation and a Young Scholar Award from the Cyrus Tang Foundation.We thank Dr. Yang Zhao for sharing published materials (Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences) and the Cryo-EM Center of the University of Science and Technology of China for the EM facility support. We are grateful to Y. Gao and all other staff members for their technical support on cryo-EM data collection.

Volume

Issue

Article Number

100632

eISSN

2590-3462

IST-REx-ID

13209

Cite this

Xia J, Kong M, Yang Z, et al. Chemical inhibition of Arabidopsis PIN-FORMED auxin transporters by the anti-inflammatory drug naproxen. Plant Communications. 2023;4(6). doi:10.1016/j.xplc.2023.100632

Xia, J., Kong, M., Yang, Z., Sun, L., Peng, Y., Mao, Y., … Tan, S. (2023). Chemical inhibition of Arabidopsis PIN-FORMED auxin transporters by the anti-inflammatory drug naproxen. Plant Communications. Elsevier . https://doi.org/10.1016/j.xplc.2023.100632

Xia, Jing, Mengjuan Kong, Zhisen Yang, Lianghanxiao Sun, Yakun Peng, Yanbo Mao, Hong Wei, et al. “Chemical Inhibition of Arabidopsis PIN-FORMED Auxin Transporters by the Anti-Inflammatory Drug Naproxen.” Plant Communications. Elsevier , 2023. https://doi.org/10.1016/j.xplc.2023.100632.

J. Xia et al., “Chemical inhibition of Arabidopsis PIN-FORMED auxin transporters by the anti-inflammatory drug naproxen,” Plant Communications, vol. 4, no. 6. Elsevier , 2023.

Xia, Jing, et al. “Chemical Inhibition of Arabidopsis PIN-FORMED Auxin Transporters by the Anti-Inflammatory Drug Naproxen.” Plant Communications, vol. 4, no. 6, 100632, Elsevier , 2023, doi:10.1016/j.xplc.2023.100632.

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