Metformin blocks BIK1-mediated CPK28 phosphorylation and enhances plant immunity

IF 11.4 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Journal of Advanced Research Pub Date : 2025-02-01 DOI:10.1016/j.jare.2024.02.025

Yazhou Bao , Qian Zhang , Hai Zhu , Yong Pei , Yaning Zhao , Yixin Li , Peiyun Ji , Dandan Du , Hao Peng , Guangyuan Xu , Xiaodan Wang , Zhiyuan Yin , Gan Ai , Xiangxiu Liang , Daolong Dou

{"title":"Metformin blocks BIK1-mediated CPK28 phosphorylation and enhances plant immunity","authors":"Yazhou Bao , Qian Zhang , Hai Zhu , Yong Pei , Yaning Zhao , Yixin Li , Peiyun Ji , Dandan Du , Hao Peng , Guangyuan Xu , Xiaodan Wang , Zhiyuan Yin , Gan Ai , Xiangxiu Liang , Daolong Dou","doi":"10.1016/j.jare.2024.02.025","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><div>Metformin (MET), derived from <em>Galega officinalis</em>, stands as the primary first-line medication for the treatment of type 2 diabetes (T2D). Despite its well-documented benefits in mammalian cellular processes, its functions and underlying mechanisms in plants remain unclear.</div></div><div><h3>Objectives</h3><div>This study aimed to elucidate MET’s role in inducing plant immunity and investigate the associated mechanisms.</div></div><div><h3>Methods</h3><div>To investigate the impact of MET on enhancing plant immune responses, we conducted assays measuring defense gene expression, reactive oxygen species (ROS) accumulation, mitogen-activated protein kinase (MAPK) phosphorylation, and pathogen infection. Additionally, surface plasmon resonance (SPR) and microscale thermophoresis (MST) techniques were employed to identify MET targets. Protein-protein interactions were analyzed using a luciferase complementation assay and a co-immunoprecipitation assay.</div></div><div><h3>Results</h3><div>Our findings revealed that MET boosts plant disease resistance by activating MAPKs, upregulating the expression of downstream defense genes, and fortifying the ROS burst. CALCIUM-DEPENDENT PROTEIN KINASE 28 (CPK28) was identified as a target of MET. It inhibited the interaction between BOTRYTIS-INDUCED KINASE 1 (BIK1) and CPK28, blocking CPK28 threonine 76 (T76) transphosphorylation by BIK1, and alleviating the negative regulation of immune responses by CPK28. Moreover, MET enhanced disease resistance in tomato, pepper, and soybean plants.</div></div><div><h3>Conclusion</h3><div>Collectively, our data suggest that MET enhances plant immunity by blocking BIK1-mediated CPK28 phosphorylation.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"68 ","pages":"Pages 31-41"},"PeriodicalIF":11.4000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785555/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Advanced Research","FirstCategoryId":"103","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2090123224000870","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}

引用次数: 0

Abstract

Introduction

Metformin (MET), derived from Galega officinalis, stands as the primary first-line medication for the treatment of type 2 diabetes (T2D). Despite its well-documented benefits in mammalian cellular processes, its functions and underlying mechanisms in plants remain unclear.

Objectives

This study aimed to elucidate MET’s role in inducing plant immunity and investigate the associated mechanisms.

Methods

To investigate the impact of MET on enhancing plant immune responses, we conducted assays measuring defense gene expression, reactive oxygen species (ROS) accumulation, mitogen-activated protein kinase (MAPK) phosphorylation, and pathogen infection. Additionally, surface plasmon resonance (SPR) and microscale thermophoresis (MST) techniques were employed to identify MET targets. Protein-protein interactions were analyzed using a luciferase complementation assay and a co-immunoprecipitation assay.

Results

Our findings revealed that MET boosts plant disease resistance by activating MAPKs, upregulating the expression of downstream defense genes, and fortifying the ROS burst. CALCIUM-DEPENDENT PROTEIN KINASE 28 (CPK28) was identified as a target of MET. It inhibited the interaction between BOTRYTIS-INDUCED KINASE 1 (BIK1) and CPK28, blocking CPK28 threonine 76 (T76) transphosphorylation by BIK1, and alleviating the negative regulation of immune responses by CPK28. Moreover, MET enhanced disease resistance in tomato, pepper, and soybean plants.

Conclusion

Collectively, our data suggest that MET enhances plant immunity by blocking BIK1-mediated CPK28 phosphorylation.

Abstract Image

查看原文本刊更多论文

二甲双胍可阻断 BIK1 介导的 CPK28 磷酸化，增强植物免疫力。

简介二甲双胍（MET）提取自 Galega officinalis，是治疗 2 型糖尿病（T2D）的主要一线药物。尽管二甲双胍在哺乳动物细胞过程中的益处有据可查，但其在植物中的功能和潜在机制仍不清楚：本研究旨在阐明 MET 在诱导植物免疫中的作用，并研究其相关机制：为了研究 MET 对增强植物免疫反应的影响，我们进行了防御基因表达、活性氧（ROS）积累、丝裂原活化蛋白激酶（MAPK）磷酸化和病原体感染的测定。此外，我们还采用了表面等离子体共振（SPR）和微尺度热泳（MST）技术来识别 MET 靶标。利用荧光素酶互补试验和共免疫沉淀试验分析了蛋白质与蛋白质之间的相互作用：结果：我们的研究结果表明，MET通过激活MAPKs、上调下游防御基因的表达以及增强ROS爆发来提高植物的抗病性。钙独立蛋白激酶 28（CPK28）被确定为 MET 的靶标。MET抑制了BOTRYTIS-INDUCED KINASE 1（BIK1）和CPK28之间的相互作用，阻止了CPK28苏氨酸76（T76）被BIK1转磷酸化，减轻了CPK28对免疫反应的负调控。此外，MET 还能增强番茄、辣椒和大豆植株的抗病性：总之，我们的数据表明，MET 可通过阻断 BIK1 介导的 CPK28 磷酸化增强植物免疫力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Advanced Research Multidisciplinary-Multidisciplinary

CiteScore

21.60

自引率

0.90%

发文量

280

审稿时长

12 weeks

期刊介绍： Journal of Advanced Research (J. Adv. Res.) is an applied/natural sciences, peer-reviewed journal that focuses on interdisciplinary research. The journal aims to contribute to applied research and knowledge worldwide through the publication of original and high-quality research articles in the fields of Medicine, Pharmaceutical Sciences, Dentistry, Physical Therapy, Veterinary Medicine, and Basic and Biological Sciences. The following abstracting and indexing services cover the Journal of Advanced Research: PubMed/Medline, Essential Science Indicators, Web of Science, Scopus, PubMed Central, PubMed, Science Citation Index Expanded, Directory of Open Access Journals (DOAJ), and INSPEC.