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

Shannon Kelleher, Bo Lönnerdal

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

During lactation, a substantial amount of Zn2+ is transferred by the mammary gland from the maternal circulation into milk; thus secretory mammary epithelial cells must tightly regulate Zn2+ transport to ensure optimal Zn2+ transfer to the suckling neonate. To date, six Zn2+ 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 Zn2+ 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 Zn2+ import, which may reflect the unique requirement for Zn2+ of this highly specialized cell type and thus provides a physiological explanation for the restricted tissue distribution of this Zn 2+ importer.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume288
Issue number5 57-5
DOIs
StatePublished - May 1 2005

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Prolactin
Zinc
Breast
Epithelial Cells
Human Mammary Glands
Tissue
Phenotype
Confocal microscopy
Gene Silencing
Cell death
Tissue Distribution
Lactation
Confocal Microscopy
Milk
Cell Death
Genes
Mothers
Proteins

All Science Journal Classification (ASJC) codes

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

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Zip3 plays a major role in zinc uptake into mammary epithelial cells and is regulated by prolactin. / Kelleher, Shannon; Lönnerdal, Bo.

In: American Journal of Physiology - Cell Physiology, Vol. 288, No. 5 57-5, 01.05.2005.

Research output: Contribution to journalArticle

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