Mammalian zinc transporters.

Genes that are involved in mammalian zinc transport recently have been cloned. These all predict proteins with multiple membrane spanning regions, and most have a histidine-rich intracellular loop. ZnT-1 was the first cloned and is associated with zinc efflux. It is found in all tissues examined, and, at least in some, ZnT-1 expression is regulated by dietary zinc intake. In enterocytes of the small intestine and renal tubular cells, ZnT-1 is localized to the basolateral membrane, suggesting an orientation that is consistent with zinc absorption/retention. ZnT-2 is also an exporter and may be involved in zinc efflux or uptake into vesicles in intestine, kidney, and testis. ZnT-3 is involved in zinc uptake into vesicles in neurons and possibly in testis. ZnT-4 is also an exporter and is highly expressed in mammary gland and brain. The divalent cation transporter 1 (DCT1) is regulated by iron, but exhibits transport activity for a number of trace elements including zinc. Description of a family of zinc transporters bridges the integrative and reductionist approach to the study of zinc metabolism. Other members of this transporter family may emerge. Many of these may be regulated by zinc, and some may respond to immune challenge, oxidative stress, and competing metals in the dietary supply. Collectively, description of transporters that influence cellular zinc uptake and efflux will provide a clearer understanding of the molecular events that regulate zinc absorption and homeostasis.