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; Wang, Hong; Wei, Ying; Gao, Yongxiang; Friml, Jiřı́; Weng, Jianping; Liu, Xin; Sun, Linfeng; Tan, Shutang

doi:10.1016/j.xplc.2023.100632

Cited by 4 publications

(4 citation statements)

References 68 publications

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Section: Discussionmentioning

confidence: 98%

“…Since the V583 residue is required for the docking of NPA, but not for IAA, we assumed that the P584L substitution near the V583 residue reduces competition of NPA with IAA (Figure 4C‐E). In a recent report, higher concentrations of naproxen, an anti‐inflammatory drug, inhibit root growth like NPA (Xia et al, 2023). Naproxen and NPA may have a similar binding pattern with PIN1: the naphthalene groups of naproxen are stacked between the hydrophobic residues of PIN1, including the I582 and V583 residues (Xia et al, 2023).…”

Section: Discussionmentioning

confidence: 99%

“…In a recent report, higher concentrations of naproxen, an anti‐inflammatory drug, inhibit root growth like NPA (Xia et al, 2023). Naproxen and NPA may have a similar binding pattern with PIN1: the naphthalene groups of naproxen are stacked between the hydrophobic residues of PIN1, including the I582 and V583 residues (Xia et al, 2023). In future investigations, determining the binding affinity of IAA and NPA inside the PIN1 P584L protein using methods like isothermal titration calorimetry and surface plasma resonance is necessary.…”

Section: Discussionmentioning

confidence: 99%

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A unique mutation in PIN‐FORMED1 and a genetic pathway for reduced sensitivity of Arabidopsis roots to N‐1‐naphthylphthalamic acid

Huang,

Chen,

Yang

et al. 2023

Physiologia Plantarum

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The small chemical N‐1‐naphthylphthalamic acid (NPA) has long been used as a polar auxin transport inhibitor. Recent biochemical and structural investigations have revealed that this molecule competes with the auxin IAA (indole‐3‐acetic acid) inside the PIN‐FORMED auxin efflux carriers. However, the existence of any mutations in PIN family proteins capable of uncoupling the docking of IAA from NPA remains unclear. We report that Arabidopsis thaliana seedlings overexpressing SMALL AUXIN UP RNA 41 were hypersensitive to NPA‐induced root elongation inhibition. We mutagenized this line to improve the genetic screening efficiency for NPA hyposensitivity mutants. Using bulked segregation analysis and mapping‐by‐sequencing assessment of these mutants, we identified a core genetic pathway for NPA‐induced root elongation inhibition, including genes required for auxin biosynthesis, transportation, and signaling. To evaluate specific changes of auxin signaling activity in mutant roots before and after NPA treatment, the DR5::GFP/DR5::YFP markers were introduced and observed. Most importantly, we discovered a unique mutation in the PIN1 protein, substituting a proline residue with leucine at position 584, leading to a loss of NPA sensitivity while keeping the auxin efflux capacity. Transforming the null mutant pin1‐201 with the PIN1::PIN1P584L‐GFP fusion construct rescued the PIN1 function and provided NPA hyposensitivity. The proline residue is predicted to be adjacent to a hinge in the middle region of the ninth transmembrane helix of PIN1 and is conserved from moss to higher plants. Our work may bring new insights into the engineering of NPA‐resistant PINs for auxin biology studies.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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A unique mutation in PIN‐FORMED1 and a genetic pathway for reduced sensitivity of Arabidopsis roots to N‐1‐naphthylphthalamic acid

Huang,

Chen,

Yang

et al. 2023

Physiologia Plantarum

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“…To prepare samples for the ITC assay, WT, mutant ABCB19, and WT ABCG25 proteins were reconstituted into the polymer amphipols as previously described ( 74 ). Briefly, purified proteins were incubated with amphipol A8-35 (Anatrace) at a 1:3 (w/w) ratio at 4°C for 4 hours with gentle rotation.…”

Section: Methodsmentioning

confidence: 99%

Structure and function of the Arabidopsis ABC transporter ABCB19 in brassinosteroid export

Ying,

Wang,

Wei

et al. 2024

Science

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Brassinosteroids are steroidal phytohormones that regulate plant development and physiology, including adaptation to environmental stresses. Brassinosteroids are synthesized in the cell interior but bind receptors at the cell surface, necessitating a yet to be identified export mechanism. Here, we show that a member of the ATP-binding cassette (ABC) transporter superfamily, ABCB19, functions as a brassinosteroid exporter. We present its structure in both the substrate-unbound and the brassinosteroid-bound states. Bioactive brassinosteroids are potent activators of ABCB19 ATP hydrolysis activity, and transport assays showed that ABCB19 transports brassinosteroids. In Arabidopsis thaliana , ABCB19 and its close homolog, ABCB1, positively regulate brassinosteroid responses. Our results uncover an elusive export mechanism for bioactive brassinosteroids that is tightly coordinated with brassinosteroid signaling.

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Protein post-translational modifications in auxin signaling

Cui

Wang

et al. 2024

Journal of Genetics and Genomics

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

Cited by 4 publications

References 68 publications

A unique mutation in PIN‐FORMED1 and a genetic pathway for reduced sensitivity of Arabidopsis roots to N‐1‐naphthylphthalamic acid

A unique mutation in PIN‐FORMED1 and a genetic pathway for reduced sensitivity of Arabidopsis roots to N‐1‐naphthylphthalamic acid

Structure and function of the Arabidopsis ABC transporter ABCB19 in brassinosteroid export

Protein post-translational modifications in auxin signaling

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