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Am J Physiol Cell Physiol (January 5, 2005). doi:10.1152/ajpcell.00471.2004
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Submitted on September 22, 2004
Accepted on December 29, 2004

Zip3 plays a major role in zinc uptake into mammary epithelial cells and is regulated by prolactin

Shannon L. Kelleher1* and Bo Lonnerdal1

1 Nutrition, University of California Davis, Davis, CA, USA

* To whom correspondence should be addressed. E-mail: slkelleher{at}ucdavis.edu.

During lactation, a substantial amount of zinc (Zn) is transferred by the mammary gland from maternal circulation into milk, thus secretory mammary epithelial cells must tightly regulate Zn transport to ensure optimal Zn transfer to the suckling neonate. To date, six Zn import proteins (Zip1-6) have been identified; however, Zip3 expression is restricted to tissues with unique requirements for Zn such as the mammary gland which suggests it may play a specialized role in this tissue. Herein we have used a unique mammary epithelial cell model (HC11) to characterize the role of Zip3 in mammary epithelial cell Zn 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 65Zn transport was higher in secreting cells, while gene silencing of Zip3 decreased 65Zn 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 import which may reflect the unique requirement for Zn of this highly specialized cell type and thus provides a physiological explanation for the restricted tissue distribution of this Zn importer.




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