Krishnan Karthik, Askew David S
Department of Pathology & Laboratory Medicine, University of Cincinnati, Cincinnati, OH 45267-0529.
Fungal Biol Rev. 2014 Oct 1;28(2-3):29-35. doi: 10.1016/j.fbr.2014.07.001.
The gateway to the secretory pathway is the endoplasmic reticulum (ER), an organelle that is responsible for the accurate folding, post-translational modification and final assembly of up to a third of the cellular proteome. When secretion levels are high, errors in protein biogenesis can lead to the accumulation of abnormally folded proteins, which threaten ER homeostasis. The unfolded protein response (UPR) is an adaptive signaling pathway that counters a buildup in misfolded and unfolded proteins by increasing the expression of genes that support ER protein folding capacity. Fungi, like other eukaryotic cells that are specialized for secretion, rely upon the UPR to buffer ER stress caused by fluctuations in secretory demand. However, emerging evidence is also implicating the UPR as a central regulator of fungal pathogenesis. In this review, we discuss how diverse fungal pathogens have adapted ER stress response pathways to support the expression of virulence-related traits that are necessary in the host environment.
分泌途径的入口是内质网(ER),这是一种细胞器,负责多达三分之一的细胞蛋白质组的精确折叠、翻译后修饰和最终组装。当分泌水平较高时,蛋白质生物合成过程中的错误会导致异常折叠蛋白质的积累,这会威胁内质网的稳态。未折叠蛋白反应(UPR)是一种适应性信号通路,通过增加支持内质网蛋白质折叠能力的基因的表达来应对错误折叠和未折叠蛋白质的积累。与其他专门用于分泌的真核细胞一样,真菌依靠UPR来缓冲由分泌需求波动引起的内质网应激。然而,新出现的证据也表明UPR是真菌致病机制的核心调节因子。在这篇综述中,我们讨论了多种真菌病原体如何调整内质网应激反应途径,以支持在宿主环境中必需的与毒力相关性状的表达。