禾谷镰孢菌Rag GTPases对TOR信号途径的调控机制研究

In yeast and mammalian cell, Rag GTPases (Rag small GTP binding protein) play important roles in regulating TOR (target of rapamycin) signaling pathway, and the mechanism underlying this regulation has been clarified. However, very little information is available about functional analysis of Rag GTPases in filamentous fungi. Our previous studies showed that there exists two Rag GTPases named FgGtr1 and FgGtr2 in Fusarium graminearum, and these two Rag GTPases could interact with FgKog1 which is the key component of TOR signaling pathway. More importantly, FgGtr1 and FgGtr2 were proved to be important for mycotoxin biosynthesis and pathogenicity using target gene deletion strategy. These results indicated that Rag GTPases may be involved in TOR signaling pathway to regulate pathogenicity and mycotoxin biosynthesis. Based on current research, the objective of this project is to deeply analyze the biological functions of Rag GTPases in F. graminearum, analyze the functions of Rag GTPases complex regulating TOR signaling pathway, and clarify the mechanism of Rag GTPases regulating pathogenicity and mycotoxin biosynthesis. Results of this project will provide molecular targets for novel fungicides development and scientific basis for strategy of controlling wheat head blight and mycotoxin contamination.

Rag GTPases（Rag亚类小GTP结合蛋白）是哺乳动物和酵母中TOR（雷帕霉素靶标）信号途径的关键调控元件，且调控机制相对清楚，但丝状真菌中相关研究甚少。申请人前期研究发现禾谷镰孢菌中存在两个Rag GTPases（命名为FgGtr1和FgGtr2），它们可与TOR信号途径的关键元件 FgKog1互作，靶向基因敲除实验证实FgGtr1和FgGtr2在致病产毒中发挥重要作用，表明Rag GTPases可能参与调控TOR信号途径并在禾谷镰孢菌致病和产毒中发挥重要作用。在此基础上，本项目将深入研究禾谷镰孢菌Rag GTPases的生物学功能，分析 Rag GTPases及其互作蛋白所形成的复合体对TOR信号途径的调控作用，阐明Rag GTPases在禾谷镰孢菌致病和产毒过程中的作用机制。预期结果将为新型杀菌剂的研发提供分子靶标，为赤霉病的持续防控和毒素污染治理提供科学依据。

真核生物中TOR（雷帕霉素靶标）信号途径在营养代谢、核糖体合成和延长生命等方面起重要作用，Rag GTPases（Rag亚类小GTP结合蛋白）是TOR信号途径的关键调控元件，但目前丝状真菌中Rag GTPases对TOR信号途径的调控机制还不清楚。课题组研究发现禾谷镰刀菌中存在两个Rag GTPase（FgGtr1和FgGtr2），FgGtr1和FgGtr2直接互作，调控了禾谷镰刀菌的致病和DON毒素的合成；禾谷镰刀菌FgGtr1-FgGtr2复合体与TORC1（TOR复合体1）上的关键元件FgKog1互作，并正调控FgTORC1下游关键激酶FgSch9的磷酸化。这些结果表明，Rag GTPases参与调控禾谷镰刀菌TOR信号途径。项目同时发现了TOR信号途径下游关键元件磷酸酶复合体FgSit4-FgSap复合体调控病菌致病力与毒素合成，阐明了Rag GTPases调控TOR信号途径的具体机制。结果将为深入研究丝状真菌中TOR信号途径的调控机制，发掘TOR信号途径上的新药靶，研制既控制病害又抑制毒素的新型杀菌剂奠定坚实基础。