Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University, Kyoto 606-8502, Japan.
Int J Mol Sci. 2017 Oct 19;18(10):2179. doi: 10.3390/ijms18102179.
More than one-third of newly synthesized proteins are targeted to the early secretory pathway, which is comprised of the endoplasmic reticulum (ER), Golgi apparatus, and other intermediate compartments. The early secretory pathway plays a key role in controlling the folding, assembly, maturation, modification, trafficking, and degradation of such proteins. A considerable proportion of the secretome requires zinc as an essential factor for its structural and catalytic functions, and recent findings reveal that zinc plays a pivotal role in the function of the early secretory pathway. Hence, a disruption of zinc homeostasis and metabolism involving the early secretory pathway will lead to pathway dysregulation, resulting in various defects, including an exacerbation of homeostatic ER stress. The accumulated evidence indicates that specific members of the family of Zn transporters (ZNTs) and Zrt- and Irt-like proteins (ZIPs), which operate in the early secretory pathway, play indispensable roles in maintaining zinc homeostasis by regulating the influx and efflux of zinc. In this review, the biological functions of these transporters are discussed, focusing on recent aspects of their roles. In particular, we discuss in depth how specific ZNT transporters are employed in the activation of zinc-requiring ectoenzymes. The means by which early secretory pathway functions are controlled by zinc, mediated by specific ZNT and ZIP transporters, are also subjects of this review.
超过三分之一的新合成蛋白质被靶向到早期分泌途径，该途径由内质网（ER）、高尔基体和其他中间隔室组成。早期分泌途径在控制这些蛋白质的折叠、组装、成熟、修饰、运输和降解方面起着关键作用。相当一部分分泌蛋白需要锌作为其结构和催化功能的必需因素，最近的发现揭示了锌在早期分泌途径的功能中起着关键作用。因此，涉及早期分泌途径的锌动态平衡和代谢的破坏将导致途径失调，导致各种缺陷，包括内质网稳态应激的加剧。越来越多的证据表明，在早期分泌途径中起作用的锌转运体（ZNTs）和 Zrt-和 Irt-样蛋白（ZIPs）家族的特定成员通过调节锌的流入和流出，在维持锌动态平衡方面发挥着不可或缺的作用。在这篇综述中，讨论了这些转运体的生物学功能，重点介绍了它们作用的最新方面。特别是，我们深入讨论了特定的 ZNT 转运体如何用于激活需要锌的细胞外酶。本综述还讨论了特定的 ZNT 和 ZIP 转运体介导的锌通过早期分泌途径功能的控制方式。
