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Author Spotlight: Exploring Cellular Zinc Regulation Through ZnT1 Functionality
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Author Spotlight: Exploring Cellular Zinc Regulation Through ZnT1 Functionality

Published on: June 2, 2023

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Function, Structure, and Transport Aspects of ZIP and ZnT Zinc Transporters in Immune Cells

Bum-Ho Bin1,2, Juyeon Seo3, Sung Tae Kim4

  • 1Department of Molecular Science and Technology, College of Natural Sciences, Ajou University, Suwon 16499, Republic of Korea.

Journal of Immunology Research
|October 30, 2018
PubMed

Zinc is an important trace metal in immune systems, and zinc transporters are involved in many immune responses. Recent advances have revealed the structural and biochemical bases for zinc transport across the cell membrane, with clinical implications for the regulation of zinc homeostasis in immune cells like dendritic cells, T cells, B cells, and mast cells. In this review, we discuss the function, structure, and transport aspects of two major mammalian zinc transporter types, importers and exporters. First, Zrt-/Irt-like proteins (ZIPs) mediate the zinc influx from the extracellular or luminal side into the cytoplasm. There are 14 ZIP family members in humans. They form a homo- or heterodimer with 8 transmembrane domains and extra-/intracellular domains of various lengths. Several ZIP members show specific extracellular domains composed of two subdomains, a helix-rich domain and proline-alanine-leucine (PAL) motif-containing domain. Second, ZnT (zinc transporter) was initially identified in early studies of zinc biology; it mediates zinc efflux as a counterpart of ZIPs in zinc homeostasis. Ten family members have been identified. They show a unique architecture characterized by a Y-shaped conformation and a large cytoplasmic domain. A precise, comprehensive understanding of the structures and transport mechanisms of ZIP and ZnT in combination with mice experiments would provide promising drug targets as well as a basis for identifying other transporters with therapeutic potential.

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