大豆疫霉效应子PsAvh262挟持大豆BAG7调控寄主内质网应激的分子机制研究

Phytophthora pathogens secrete an array of specific effector proteins to manipulate host innate immunity in multiple ways to promote pathogen colonization. Our previous study shows that a Phytophthora RxLR effector targets plant BiP, the master regulators of the ER stress, to manipulate the ER stress pathways and suppress ER stress-induced programmed cell death to promote infection. Recently, we found that Phytophthora sojae effector PsAvh262 interacts with BAG7, which the BAG7 binds to BiP for manipulating the ER stress response and promotes Phytophthora infection. Here, the molecular and virulent mechanism of the PsAvh262-BAG7 interaction will be studied, including: the function of BAG7 in regulating host resistance to Phytophtora and ER stress, the impact of PsAvh262 in the translocation and cleavage of BAG7 to illustrate the binding mechanism, the role of BAG7 in the regulating ER stress and host resistance of PsAvh262 and the elucidation of the virulent mechanism of the PsAvh262-BAG7 interaction. This work focuses on how Phtophthora utilizes effector to hijack host ER stress, which will further illuminate this mechanism that effector is able to hijack and overcome host ER stress, understand the relationship between Phytophthora infection and host ER stress, and provide scientific basis for development of novel control strategies against oomycete pathogens.

疫霉菌可以分泌大量效应子到寄主细胞中，通过多种途径来操控植物抗病性进而成功致病。申请人前期研究发现大豆疫霉RxLR效应子PsAvh262能够稳定内质网应激调节因子BiP，并抑制寄主内质网应激诱导的细胞死亡，但其具体作用机制尚不清楚。近期我们发现效应子PsAvh262与内质网分子伴侣BAG7互作，而BAG7能与BiP结合调控内质网应激反应并促进疫霉菌的侵染。本项目拟通过研究PsAvh262与大豆BAG7之间的互作机制，明确BAG7在内质网应激和植物免疫中的功能，探索效应子对BAG7重定位和修饰的影响，阐明效应子PsAvh262与寄主BAG7结合的生化效应与致病机理。本研究的完成将进一步揭示疫霉菌利用效应子挟持寄主内质网应激这一致病机制，有助于认识疫霉菌侵染与寄主内质网应激调控的关系，为合理有效地开发卵菌病害控制技术奠定理论基础。

疫霉菌作为一类重要的植物病原菌，能引起农业上多种重要作物的毁灭性病害。疫霉菌可以分泌大量效应子到寄主细胞中，通过多种途径来操控植物抗病性进而成功致病。前期研究发现疫霉菌会利用效应子挟持寄主的内质网应激反应来促进自身侵染，因此研究和理解其介导的寄主感病机制以及植物识别疫霉菌触发内质网应激的分子机理至关重要。经过三年的努力，我们取得了以下进展和成果：.1) 揭示了植物内质网应激反应调控因子BAG7在与疫霉菌互作中的“双面因子”角色，当大豆BAG7定位于内质网时作为“感病因子”介导植物对疫霉菌的感病性，而在细胞核定位的BAG7则可增强植物对疫霉菌的抗病性；而疫霉菌侵染信号可以触发BAG7由感病因子向抗病因子的转变。.2) 阐明了大豆疫霉菌效应子PsAvh262可以通过促进BiP的积累将bZIP28和BAG7滞留在内质网中，阻碍bZIP28和BAG7向细胞核的转运，从而促进疫霉菌的侵染的基本机制。在此过程中，效应子PsAvh262毒性功能的发挥依赖于其保守区域的蛋白二级结构。.3) 揭示了植物识别疫霉菌侵染信号分子而激活内质网应激反应的分子机理。疫霉菌侵染信号会诱导内质网应激关键调节因子NAC089由内质网向细胞核的转运，直接诱导细胞死亡介导对疫霉菌的抗性；而植物免疫共受体BAK1介导了NAC089的这一转运过程。.4) 应邀综述了病原菌效应子挟持寄主内质网作为其致病策略的作用机制。.5) 根据疫霉菌的致病特性，构建了抑菌蛋白精确靶向疫霉菌丝的植物抗疫病新策略，并成功应用于大豆和马铃薯等作物，赋予其增强的、广谱的抗疫病性。. 受项目资助，我们在《Molecular Plant》、《Plant Journal》、《Journal of Experimental Botany》、《Engineering》等期刊发表论文10篇。