A Novel Selective Autophagy Pathway in Plant Immune Responses to Necrotrophic Pathogens

坏死性致病菌是一类重要的植物病原真菌和细菌，具有很强的侵袭性和广泛的寄主范围。它们主动杀死植物细胞，从死亡组织中提取营养。由于对坏死性致病菌的抗性通常由多个基因控制，因此很难培育出具有抗性的作物，因此防治坏死性致病菌引起的作物病害往往依赖于农药的施用。目前，对这类病原体耐药性的潜在分子机制的认识和理解非常有限。已知它涉及一个称为自噬的过程，在这个过程中，特定的细胞质成分被降解，这反过来又以某种方式阻止入侵的坏死细胞诱导细胞死亡。本项目旨在阐明自噬保护植物免受坏死性病原体侵害的机制。本项目的重点是植物特异性ATI3自噬受体介导的一种新的选择性自噬途径，该自噬受体通过与ATG8的相互作用被招募到自噬体中。遗传分析表明ATI3在植物抗坏死性营养物质中起关键作用。ATI3还与内质网（ER）相关降解（ERAD）中一个保守的泛素结合成分的同源物UBAC2a和UBAC2b相互作用。本项目将测试ATI3选择性自噬途径是否通过靶向有害内质网成分在植物对坏死性营养物质的免疫中发挥重要作用，从而保护植物免受病原体诱导的内质网应激介导的细胞死亡。具体目标是：(1)通过综合遗传分析，确认ATI3和UBAC2在植物抗病性中的关键作用；2)确定ATI3/ ubac2介导的选择性自噬是否保护植物细胞免受病原体诱导的内质网胁迫；3)分析内质网应激传感器IRE1和ATI3- ubac2物理相互作用在ATI3选择性自噬通路调控中的作用。该项目的目标是发现与植物对特定植物生物和非生物胁迫反应相关的选择性自噬的独特途径。详细了解自噬在植物免疫系统中的作用将有助于开发新的抗病作物策略。自噬和ERAD也与包括癌症在内的许多人类疾病有关，因此，该项目的知识将对植物世界以外的领域产生影响。该项目将为研究生提供一个强大的跨学科培训环境。项目的某些方面将被纳入培养具有分子生物学技术实践经验的本科生的课程，并在课堂上进行创造性教学。

Necrotrophic pathogens are an important group of plant pathogenic fungi and bacteria notorious for their aggressiveness and broad host range. They actively kill plant cells to extract nutrients from dead tissue. Control of crop diseases caused by necrotrophic pathogens often relies on pesticide application because resistance to necrotrophic pathogens is usually controlled by multiple genes, making it difficult to breed for resistance. Presently, knowledge about, and understanding of the underlying molecular mechanisms for resistance to this type of pathogen is very limited. It is known to involve a process called autophagy in which specific cytoplasmic constituents are degraded, which in turn somehow prevents the invading necrotroph from inducing cell death. This project aims to elucidate the mechanism by which autophagy protects plants from necrotrophic pathogens.At the focus of this project is a novel selective autophagy pathway mediated by the plant-specific ATI3 autophagy receptor, which is recruited to autophagosomes through interaction with ATG8. Genetic analyses suggest ATI3 plays a critical role in plant resistance to necrotrophs. ATI3 also interacts with UBAC2a and UBAC2b, homologs of a conserved ubiquitin-binding component of endoplasmic reticulum (ER)-associated degradation (ERAD). This project will test whether the ATI3 selective autophagy pathway plays an important role in plant immunity to necrotrophs by targeting deleterious ER constituents, thereby protecting against pathogen-induced, ER stress-mediated cell death. Specific objectives are to (1) confirm the critical role of ATI3 and UBAC2 in plant disease resistance through comprehensive genetic analysis; 2) determine whether the ATI3/UBAC2-mediated selective autophagy protects plant cells against pathogen-induced ER stress; and 3) analyze the role of the ER stress sensor IRE1 and the physical ATI3-UBAC2 interaction in the regulation of the ATI3 selective autophagy pathway. The goal of the project is the discovery of distinct pathways of selective autophagy associated with plant responses to specific plant biotic and abiotic stresses. Detailed knowledge on the role of autophagy in plant immune systems will lead to development of novel strategies for creating disease resistant crops. Autophagy and ERAD are also involved in many diseases in humans including cancers and, therefore, the knowledge from the project will have implications beyond the plant world. This project will provide a strong interdisciplinary training environment for graduate students. Some aspects of project will be incorporated into programs for training undergraduate students with hands-on experience in molecular biology techniques and for creative teaching in classrooms.