MAMMALIAN ZINC TRANSPORTERS

Genes that are involved in mammalian zinc transport recently have been cloned. These all predict proteins with multiple membrane spanning re gions, and most have a histidine-rich intracellular loop. ZnT-1 was th e 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 ren al tubular cells, ZnT-1 is localized to the basolateral membrane, sugg esting an orientation that is consistent with zinc absorption/retentio n. ZnT-2 is also an exporter and may be involved in zinc efflux or upt ake 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 e xhibits transport activity for a number of trace elements including zi nc. Description of a family of zinc transporters bridges the integrati ve and reductionist approach to the study of zinc metabolism. Other me mbers of this transporter family may emerge. Many of these may be regu lated by zinc, and some may respond to immune challenge, oxidative str ess, and competing metals in the dietary supply. Collectively, descrip tion of transporters that influence cellular zinc uptake and efflux wi ll provide a clearer understanding of the molecular events that regula te zinc absorption and homeostasis.