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

• Published in: Journal of Immunology Research Vol. 2018; no. 2018; pp. 1 - 9
• Main Authors: Bin, Bum-Ho, Kim, Sung Tae, Seo, Juyeon
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01.01.2018; Hindawi; John Wiley & Sons, Inc; Hindawi Limited; Wiley
• Subjects: Alanine; Animals; Antigens; Apoptosis; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cation Transport Proteins - genetics; Cation Transport Proteins - metabolism; Cell membranes; Conformation; Cytokines; Cytoplasm; Dendritic cells; Diabetes; Homeostasis; Humans; Immune System; Immunity, Cellular; Immunology; Ion Transport; Kinases; Leucine; Lymphocytes; Lymphocytes B; Lymphocytes T; Mammals; Mast cells; Mice; Molecular Structure; Molecular Targeted Therapy; Mutation; Phosphatase; Phosphorylation; Proline; Protein Conformation; Proteins; Repressor Proteins - genetics; Repressor Proteins - immunology; Repressor Proteins - metabolism; Review; Roles; Structure-function relationships; T cell receptors; Transmembrane domains; Zinc; Zinc - metabolism; Zinc transporter; Zinc Transporter 8 - genetics; Zinc Transporter 8 - metabolism; United States > US
• ISSN: 2314-8861; 2314-7156
• DOI: 10.1155/2018/9365747

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.