Zinc transporter 5

Intracellular zinc homeostasis is regulated by zinc-binding proteins and zinc transporters (Rink et al. 2007). The zinc transporters are encoded by two SLC ("solute linked carrier") gene families:

• Members of the SLC39 family (Zip, "Zrt- and Irt-like proteins") increase the cytoplasmic zinc level by zinc uptake.
• Members of the SLC30 family (ZnT, zinc transporter/exporter; CDF family, cation diffusion facilitator) lower intracellular zinc concentrations by transporting zinc out of the cell or into vesicular structures. So far, 15 Zips and 9 ZnTs have been detected in various human cells.

ZnT-5 is expressed in many tissues, with the highest expression in pancreatic beta cells. There the zinc is transported into the insulin-containing, secretory granules (Kambe et al. 2002). Furthermore, ZnT-5 is also involved in zinc transport into the Golgi apparatus and vesicles (Kambe et al. 2002). Furthermore, ZnT-5 plays a fundamental role in the maturation of osteoblasts and in the maintenance of normal heart function (Inoue et al. 2002). Experiments have shown that high zinc concentrations result in increased expression in the human colon adenocarcinoma cell line Caco-2, while no changes were observed in placental cells and in the human cervical carcinoma cell line HeLa (Ford, 2004). In contrast, zinc deficiency leads to low mRNA levels in THP-1 cells and increased expression in HeLa cells.

1. Chimienti F et al (2005) ZnT-8, a pancreatic beta-cell-specific zinc transporter. Biometals 18: 313-317.
2. Chowanadisai W et al (2006) Identification of a mutation in SLC30A2 (ZnT-2) in women with low milk zinc concentration that results in transient neonatal zinc deficiency. J Biol Chem 281: 39699-39707.
3. Devergnas S et al (2004) Differential regulation of zinc efflux transporters ZnT-1, ZnT-5 and ZnT-7 gene expression by zinc levels: a real-time RT-PCR study. Biochem. Pharmacol 68: 699-709.
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7. Kambe T et al (2004) Overview of mammalian zinc transporters. Cell Mol Life Sci 61: 49-68.
8. Michalczyk AA et al. (2002) Constitutive expression of hZnT4 zinc transporters in human breast epithelial cells. Biochem J 364: 105-113.
9. Overbeck S (2008) The regulation of zinc transporters and their influence on intracellular zinc homeostasis in leukocytes. Dissertation. Publication server of RWTH Aachen University