Integrative aspects of zinc transporters

Cells maintain zinc concentrations with relatively narrow limits, Neverthel ess, physiologically relevant changes in free Zn(ll) pools or changes in Zn bound to specific ligands or within vesicles may occur without a major cha nge in total cellular zinc concentrations. The task of maintaining such lev els rests in part with zinc transporter proteins. The genes for some putati ve zinc transporters have recently been cloned. As of this time, most have not been directly shown to transport zinc in functional studies, albeit evi dence is strong that they have such a function. Zinc transporter (ZnT)-1 wa s identified as a rescue agent for cells maintained in very high extracellu lar zinc conditions; therefore, ZnT-1 has been suggested to function as an exporter. ZnT-1 is expressed in a variety of tissues, including intestine, kidney and liver. Intestinal expression is regional, being much greater in duodenum and jejunum and in villus versus crypt cells. Immunolocalization p laces ZnT-I at the basolateral membrane of intestinal enterocytes and epith elial cells of the distal renal tubules. Regulation of ZnT-1 mRNA and ZnT-1 protein does not change markedly with changes in dietary zinc level except when a large single oral zinc supplement is provided. ZnT-I is induced by transient ischemia of the forebrain, ZnT-2 and ZnT-3 may function in tissue -specific vesicular zinc transport. ZnT-4 is believed to be abundant in mam mary gland and may be associated with zinc secretion into milk. A mutation of the ZnT-4 gene may account for the lethal milk (Im) syndrome. The putati ve zinc transporters identified thus far appear to have characteristics com mensurate with functions in integrative zinc acquisition and homeostasis.