The chaperone-mediated sequestration of misfolded proteins into specialized quality control compartments represents an important strategy for maintaining protein homeostasis in response to stress. However, precisely how this process is controlled in time and subcellular space and integrated with the cell's protein refolding and degradation pathways, remains unclear. We set out to understand how aggregated proteins are managed during infection-related development by a globally devastating plant pathogenic fungus, and to determine how impaired protein quality control impacts upon cellular differentiation and pathogenesis in this system. Here we show that in the absence of Hsp104 disaggregase activity aggregated proteins are spatially sequestered into quality control compartments within conidia, but not within terminally differentiated infection cells, and thus spatial protein quality control is cell-type dependent. We demonstrate that impaired aggregate resolution results in a short-term developmental penalty but has no significant impact upon appressorium function. Lastly, we show that, somewhat unexpectedly, the autophagy machinery is necessary for the normal formation and compartmentalization of protein aggregates. Taken together, our findings provide important new insight into spatial protein quality control during the process of terminal cellular differentiation by a globally important model eukaryote and reveals a new level of interplay between major proteostasis pathways.

伴侣蛋白介导的将错误折叠的蛋白质螯合到专门的质量控制区室中代表了一种重要的策略，该策略可维持蛋白质对压力的动态平衡。但是，究竟如何在时间和亚细胞空间中控制该过程以及如何与细胞的蛋白质复性和降解途径整合尚不清楚。我们着手了解在具有破坏力的全球植物致病真菌感染相关的发育过程中如何管理聚集的蛋白质，并确定受损的蛋白质质量控​​制如何影响该系统中的细胞分化和发病机理。在这里，我们显示，在没有Hsp104脱氢酶活性的情况下，聚集的蛋白质在空间上被隔离在分生孢子内的质量控制区中，但不在最终分化的感染细胞内，因此空间蛋白质量控制取决于细胞类型。我们证明受损的总分辨率导致短期的发育损失，但对前肢功能没有显着影响。最后，我们显示出，出乎意料的是，自噬机制对于正常的蛋白质聚集体形成和分隔是必需的。综上所述，我们的发现为全球重要的真核生物终末细胞分化过程中的空间蛋白质质量控​​制提供了重要的新见解，并揭示了主要蛋白质稳态途径之间相互作用的新水平。我们证明受损的总分辨率导致短期的发育损失，但对前肢功能没有显着影响。最后，我们显示出，出乎意料的是，自噬机制对于正常的蛋白质聚集体形成和分隔是必需的。综上所述，我们的发现为全球重要的真核生物终末细胞分化过程中的空间蛋白质质量控​​制提供了重要的新见解，并揭示了主要蛋白质稳态途径之间相互作用的新水平。我们证明受损的总分辨率导致短期的发育损失，但对前肢功能没有显着影响。最后，我们显示出，出乎意料的是，自噬机制对于正常的蛋白质聚集体形成和分隔是必需的。综上所述，我们的发现为全球重要的真核生物终末细胞分化过程中的空间蛋白质质量控​​制提供了重要的新见解，并揭示了主要蛋白质稳态途径之间相互作用的新水平。