An oomycete effector subverts host vesicle trafficking to channel starvation-induced autophagy to the pathogen interface.
An oomycete effector subverts host vesicle trafficking to channel starvation-induced autophagy to the pathogen interface.
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DOI：
10.7554/elife.65285
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发表时间：
2021-08-23
期刊：
影响因子：
7.7
通讯作者：
Bozkurt TO
中科院分区：
文献类型：
--
作者：
Pandey P;Leary AY;Tumtas Y;Savage Z;Dagvadorj B;Duggan C;Yuen EL;Sanguankiattichai N;Tan E;Khandare V;Connerton AJ;Yunusov T;Madalinski M;Mirkin FG;Schornack S;Dagdas Y;Kamoun S;Bozkurt TO
真核细胞利用自噬来消灭入侵的微生物。反过来，病原体进化出效应器蛋白来对抗抗菌素自噬。适应的病原体是如何利用自噬来谋取自身利益的，目前还知之甚少。爱尔兰饥荒病原体马铃薯晚疫病菌分泌效应蛋白PexRD54，该蛋白选择性地激活一条未知的植物自噬途径，从而拮抗病原体界面上的抗微生物自噬。在这里，我们证明了PexRD54通过将小GTP酶Rab8a修饰的小泡与核心自噬蛋白ATG8CL标记的自噬间隔连接起来，诱导自噬小体的形成。Rab8a是病原体触发和饥饿诱导的自噬所必需的，但不是抗菌剂自噬所必需的，这揭示了选择性自噬的特定运输途径。通过颠覆Rab8a介导的囊泡运输，PexRD54利用脂滴促进转移到病原体摄食部位的自噬小体的生物发生。综上所述，我们表明PexRD54模拟饥饿诱导的自噬来颠覆宿主-病原体界面的内膜运输，揭示了效应器如何桥接不同的宿主隔间以加快定植。这种被称为致病疫霉的微小真菌生物，由于其长丝深入猎物，在人类历史上产生了不成比例的影响。它依附于植物并以它们的细胞为食，导致了大规模的饥饿事件，如爱尔兰或高地土豆饥荒。许多特殊的蛋白质让寄生虫完成了它的壮举。例如，PexRD54帮助致病疫霉劫持了一种称为自噬的细胞过程。健康的细胞使用这种“自食”机制来分解入侵者或回收它们的成分，例如当它们需要特定的营养时。这一过程是由分子事件的各种途径启动的，这些分子事件导致装满货物的特定囊状物被运输到专门的隔间进行回收。PexRD54可以通过激活其中一个植物自噬途径来接管这一机制，引导细胞形成自噬小泡，然后疫霉可能会用这些小泡来觅食或破坏抗菌成分。人们对这种情况的原因或原因仍知之甚少。为了研究这些问题，Pandey，Leary等人。使用了基因和显微技术的组合，跟踪了PexRD54在致病疫霉感染烟草相关植物时如何改变自噬。结果表明，PexRD54通过连接两种蛋白质发挥作用：一种存在于充满货物的细胞囊泡上，另一种存在于寄生虫周围的自噬结构上。这使得PexRD54可以将小泡引导到致病疫霉的摄食部位，这样寄生虫就有可能转移营养物质。Pandey，Leary等人。然后又开发了一种名为AIM肽的分子，它可以通过模仿PexRD54的一部分来阻止自噬。这些结果有助于更好地掌握一种关键疾病是如何影响作物的，可能会导致在不使用杀虫剂的情况下保护植物的新方法。他们还揭示了自噬：最终，对这一基本生物过程的更深入了解可能会使植物能够适应不断变化的环境。
Eukaryotic cells deploy autophagy to eliminate invading microbes. In turn, pathogens have evolved effector proteins to counteract antimicrobial autophagy. How adapted pathogens co-opt autophagy for their own benefit is poorly understood. The Irish famine pathogen Phytophthora infestans secretes the effector protein PexRD54 that selectively activates an unknown plant autophagy pathway that antagonizes antimicrobial autophagy at the pathogen interface. Here, we show that PexRD54 induces autophagosome formation by bridging vesicles decorated by the small GTPase Rab8a with autophagic compartments labeled by the core autophagy protein ATG8CL. Rab8a is required for pathogen-triggered and starvation-induced but not antimicrobial autophagy, revealing specific trafficking pathways underpin selective autophagy. By subverting Rab8a-mediated vesicle trafficking, PexRD54 utilizes lipid droplets to facilitate biogenesis of autophagosomes diverted to pathogen feeding sites. Altogether, we show that PexRD54 mimics starvation-induced autophagy to subvert endomembrane trafficking at the host-pathogen interface, revealing how effectors bridge distinct host compartments to expedite colonization. With its long filaments reaching deep inside its prey, the tiny fungi-like organism known as Phytophthora infestans has had a disproportionate impact on human history. Latching onto plants and feeding on their cells, it has caused large-scale starvation events such as the Irish or Highland potato famines. Many specialized proteins allow the parasite to accomplish its feat. For instance, PexRD54 helps P. infestans hijack a cellular process known as autophagy. Healthy cells use this ‘self-eating’ mechanism to break down invaders or to recycle their components, for example when they require specific nutrients. The process is set in motion by various pathways of molecular events that result in specific sac-like ‘vesicles’ filled with cargo being transported to specialized compartments for recycling. PexRD54 can take over this mechanism by activating one of the plant autophagy pathways, directing cells to form autophagic vesicles that Phytophthora could then possibly use to feed on or to destroy antimicrobial components. How or why this is the case remains poorly understood. To examine these questions, Pandey, Leary et al. used a combination of genetic and microscopy techniques and tracked how PexRD54 alters autophagy as P. infestans infects a tobacco-related plant. The results show that PexRD54 works by bridging two proteins: one is present on cellular vesicles filled with cargo, and the other on autophagic structures surrounding the parasite. This allows PexRD54 to direct the vesicles to the feeding sites of P. infestans so the parasite can potentially divert nutrients. Pandey, Leary et al. then went on to develop a molecule called the AIM peptide, which could block autophagy by mimicking part of PexRD54. These results help to better grasp how a key disease affects crops, potentially leading to new ways to protect plants without the use of pesticides. They also shed light on autophagy: ultimately, a deeper understanding of this fundamental biological process could allow the development of plants which can adapt to changing environments.