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Int. J. Mol. Sci. 2017, 18(10), 2179; https://doi.org/10.3390/ijms18102179

Understanding the Contribution of Zinc Transporters in the Function of the Early Secretory Pathway

Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University, Kyoto 606-8502, Japan
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Received: 8 September 2017 / Revised: 12 October 2017 / Accepted: 15 October 2017 / Published: 19 October 2017
(This article belongs to the Special Issue Zinc Signaling in Physiology and Pathogenesis)
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Abstract

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. View Full-Text
Keywords: ZNT/Solute carrier family 30 member (SLC30A); ZIP/SLC39A; early secretory pathway; ER stress; unfolded protein response (UPR); zinc-requiring ectoenzymes; tissue non-specific alkaline phosphatase (TNAP); metallation ZNT/Solute carrier family 30 member (SLC30A); ZIP/SLC39A; early secretory pathway; ER stress; unfolded protein response (UPR); zinc-requiring ectoenzymes; tissue non-specific alkaline phosphatase (TNAP); metallation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Kambe, T.; Matsunaga, M.; Takeda, T.-A. Understanding the Contribution of Zinc Transporters in the Function of the Early Secretory Pathway. Int. J. Mol. Sci. 2017, 18, 2179.

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