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

• Published in: Plant communications Vol. 4; no. 6; p. 100632
• Main Authors: Xia, Jing, Kong, Mengjuan, Yang, Zhisen, Sun, Lianghanxiao, Peng, Yakun, Mao, Yanbo, Wei, Hong, Ying, Wei, Gao, Yongxiang, Friml, Jiří, Weng, Jianping, Liu, Xin, Sun, Linfeng, Tan, Shutang
• Format: Journal Article
• Language: English
• Published: China Elsevier Inc 13.11.2023
• Subjects: Anti-Inflammatory Agents - metabolism; Anti-Inflammatory Agents - pharmacology; Arabidopsis; Arabidopsis - metabolism; Arabidopsis Proteins - genetics; Arabidopsis Proteins - metabolism; auxin transport; Humans; Indoleacetic Acids - metabolism; Membrane Transport Proteins - genetics; Membrane Transport Proteins - metabolism; naproxen; Naproxen - metabolism; Naproxen - pharmacology; NIMA-Interacting Peptidylprolyl Isomerase - metabolism; NPA; PIN; Plants - metabolism; naproxen; PIN; auxin transport; Arabidopsis; NPA
• ISSN: 2590-3462; 2590-3462
• DOI: 10.1016/j.xplc.2023.100632

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. The phytohormone auxin is essential for almost every aspect of plant growth and development. A key feature of auxin function is its polar transport, which is controlled by PIN family transporters. This study reports that the non-steroidal anti-inflammatory drug naproxen is an inhibitor of Arabidopsis PIN proteins.