Zip3 plays a major role in zinc uptake into mammary epithelial cells and is regulated by prolactin.
During lactation, a substantial amount of Zn(2+) is transferred by the mammary gland from the maternal circulation into milk; thus secretory mammary epithelial cells must tightly regulate Zn(2+) transport to ensure optimal Zn(2+) transfer to the suckling neonate. To date, six Zn(2+) import proteins (Zip1-6) have been identified; however, Zip3 expression is restricted to tissues with unique requirements for Zn(2+), such as the mammary gland, which suggests that it may play a specialized role in this tissue. In the present study, we have used a unique mammary epithelial cell model (HC11) to characterize the role of Zip3 in mammary epithelial cell Zn(2+) transport. Confocal microscopy demonstrated that Zip3 is localized to the cell surface in mammary epithelial cells and transiently relocalized to an intracellular compartment in cells with a secretory phenotype. Total (65)Zn transport was higher in secreting cells, while gene silencing of Zip3 decreased (65)Zn uptake into mammary epithelial cells, particularly in those with a secretory phenotype. Finally, reduced expression of Zip3 ultimately resulted in cell death, indicating that mammary epithelial cells have a unique requirement for Zip3-mediated Zn(2+) import, which may reflect the unique requirement for Zn(2+) of this highly specialized cell type and thus provides a physiological explanation for the restricted tissue distribution of this Zn(2+) importer.
Kelleher
Shannon L
SL
Dept. of Nutrition, Univ. of California, Davis, One Shields Ave., Davis, CA 95616, USA. slkelleher@ucdavis.edu
Lönnerdal
Bo
B
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D027682:Cation Transport Proteins; D002451:Cell Compartmentation / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D017136:Ion Transport / Q000502:physiology; D008321:Mammary Glands, Animal / Q000378:metabolism*; D051379:Mice; D018613:Microscopy, Confocal; D011388:Prolactin / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism*; D015033:Zinc Isotopes / Q000737:chemistry
D002352:Carrier Proteins; D027682:Cation Transport Proteins; C485744:Slc39a1 protein, mouse; C498426:Slc39a3 protein, mouse; D015033:Zinc Isotopes; D011388:Prolactin; D015032:Zinc