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A novel zinc-regulated human zinc transporter, hZTL1, is localized to the enterocyte apical membrane

Lookup NU author(s): Professor Ruth Valentine, Dr Graham Christie, Sion Phillips, Rachel Russi, Professor John Mathers, Professor Dianne Ford


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Zinc is essential to a wide range of cellular processes; therefore, it is important to elucidate the molecular mechanisms of zinc homeostasis. To date, no zinc transporters expressed at the enterocyte apical membrane, and so essential to mammalian zinc homeostasis, have been discovered. We identified hZTL1 as a human expressed sequence tag with homology to the basolateral enterocyte zinc transporter ZnT1 and deduced the fulllength cDNA sequence by PCR. The protein of 523 amino acids belongs to the cation diffusion facilitator family of membrane transporters. Unusually, the predicted topology comprises 12 rather than 6 transmembrane domains. ZTL1 mRNA was detected by reverse transcription-PCR in a range of mouse tissues. A Myc-tagged hZTL1 clone was expressed in transiently transfected polarized human intestinal Caco-2 cells at the apical membrane. Expression of hZTL1 mRNA in Caco-2 cells increased with zinc supplementation of the nutrient medium; however, in the placental cell line JAR hZTL1 appeared not to be regulated by zinc. Heterologous expression of hZTL1 in Xenopus laevis oocytes increased zinc uptake across the plasma membrane. The localization, regulatory properties, and function of hZTL1 indicate a role in regulating the absorption of dietary zinc across the apical enterocyte membrane.

Publication metadata

Author(s): Cragg RA, Christie GR, Phillips SR, Russi RM, Kury S, Mathers JC, Taylor PM, Ford D

Publication type: Article

Publication status: Published

Journal: Journal of Biological Chemistry

Year: 2002

Volume: 277

Issue: 25

Pages: 22789-22797

ISSN (print): 0021-9258

ISSN (electronic): 1083-351X

Publisher: American Society for Biochemistry and Molecular Biology, Inc.


DOI: 10.1074/jbc.M200577200

PubMed id: 11937503


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Funder referenceFunder name
D18271Biotechnology and Biological Sciences Research Council