hZip1 (hSLC39A1) regulates zinc homoeostasis in gut epithelial cells

Michalczyk, Agnes A. and Ackland, M. Leigh 2013, hZip1 (hSLC39A1) regulates zinc homoeostasis in gut epithelial cells, Genes and nutrition, vol. 8, no. 5, pp. 475-486.

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Title hZip1 (hSLC39A1) regulates zinc homoeostasis in gut epithelial cells
Author(s) Michalczyk, Agnes A.
Ackland, M. Leigh
Journal name Genes and nutrition
Volume number 8
Issue number 5
Start page 475
End page 486
Total pages 12
Publisher Springer
Place of publication Berlin, Germany
Publication date 2013
ISSN 1555-8932
1865-3499
Keyword(s) human gut
hZip1 (SLC39A1)
zinc homoeostasis
zinc transporter
Summary Zinc is an essential trace element required for enzyme catalysis, gene regulation and signal transduction. Zinc absorption takes place in the small intestine, however, the mechanisms by which cells accumulate zinc are not entirely clear. Zip1 (SLC39A1) is a predicted transmembrane protein that is postulated, but not conclusively proven to mediate zinc influx in gut cells. The aim of this study was to investigate a role for hZip1 in mediating zinc uptake in human enterocytes. Both hZip1 mRNA and protein were detected in human intestinal tissue. In non-differentiated Caco-2 human gut cells, hZip1 was partially localised to the endoplasmic reticulum. In contrast, in differentiated Caco-2 cells cultured in extracellular matrix, the hZip1 protein was located in proximity to the apical microvilli. Lack of surface antibody binding and internalisation indicated that hZip1 was not present on the plasma membrane. Functional studies to establish a role for hZip1 in cellular zinc accumulation were carried out using 65Zn. In Caco-2 cells harbouring an hZip1 overexpression construct, cellular zinc accumulation was enhanced relative to the control. Conversely, Caco-2 cells with an hZip1 siRNA construct showed reduced zinc accumulation. In summary, we show that the Caco-2 cell differentiation endorses targeting of hZip1 to a region near the apical domain. Given the absence of hZip1 at the apical plasma membrane, we propose that hZip1 may act as an intracellular sensor to regulate zinc homoeostasis in human gut cells.
Language eng
Field of Research 059999 Environmental Sciences not elsewhere classified
Socio Economic Objective 970105 Expanding Knowledge in the Environmental Sciences
HERDC Research category C1 Refereed article in a scholarly journal
Persistent URL http://hdl.handle.net/10536/DRO/DU:30055308

Document type: Journal Article
Collection: School of Life and Environmental Sciences
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