Zinc transporter 4

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.

The zinc transporter 4, ZnT-4, is expressed in intracellular vesicles. Besides expression in the kidney and intestine, this transporter is mainly found in the brain and the breast epithelium. In the mammary glands it regulates the zinc concentration in milk.

A mutation in the coding ZnT-4 gene leads to the phenotype of the so-called lethal milk mouse, in which the maternal milk does not contain enough zinc - comparable to the missense mutation in the ZnT-2 gene (Michalczyk et al. 2002). While the mRNA of ZnT-4 is not subject to changes in the liver, intestine and kidney of rats after increased oral zinc administration, it is induced in the mammary gland under zinc deficiency conditions.

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