Department of Clinical Laboratory Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China.
Department of Pathogen Biology, School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.
Front Cell Infect Microbiol. 2023 Nov 30;13:1267931. doi: 10.3389/fcimb.2023.1267931. eCollection 2023.
Copper, a vital element in various physiological processes, is transported from the gastrointestinal tract to tissues and cells through diverse copper transporters. Among these transporters, ATP7A and ATP7B play significant roles in regulating systemic copper metabolism and exhibit precise regulation in their intracellular trafficking. These transporters undergo dynamic shuttling between the trans-Golgi network (TGN) and the plasma membrane via the endocytic recycling mechanism, which involves the retromer and other associated factors. Interestingly, the antimicrobial attribute of copper implies a potential connection between microbial infection and copper metabolism. Several microbes, including , , Influenza A virus (IAV) and Zika virus (ZIKV) have been observed to impact the regulatory mechanisms of ATP7A/B, either directly or indirectly, as a means of survival. This review summarizes the key features and trafficking mechanisms of the copper transporters ATP7A/B, and examines the intricate interplay between microbes and copper metabolism. Ultimately, it highlights how microbes can perturb copper homeostasis through interactions with host factors, offering valuable insights into the mechanistic aspects of host-microbe interactions.
铜是各种生理过程中的重要元素，通过多种铜转运蛋白从胃肠道转运到组织和细胞。在这些转运蛋白中，ATP7A 和 ATP7B 在调节系统铜代谢方面发挥着重要作用，并在其细胞内运输中表现出精确的调节。这些转运蛋白通过内吞体再循环机制在高尔基网络（TGN）和质膜之间进行动态穿梭，其中涉及到 retromer 和其他相关因子。有趣的是，铜的抗菌属性意味着微生物感染和铜代谢之间可能存在联系。一些微生物，包括 、 、流感病毒（IAV）和寨卡病毒（ZIKV），已经被观察到直接或间接地影响 ATP7A/B 的调节机制，以此作为生存手段。这篇综述总结了铜转运蛋白 ATP7A/B 的关键特征和运输机制，并研究了微生物和铜代谢之间的复杂相互作用。最终，它强调了微生物如何通过与宿主因子的相互作用扰乱铜稳态，为宿主-微生物相互作用的机制方面提供了有价值的见解。
