A novel zinc-regulated human zinc transporter, hZTL1, is localized to the enterocyte apical membrane.
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 full-length 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.
Cragg
Ruth A
RA
Department of Biological and Nutritional Sciences, University of Newcastle, Kings Rd., Newcastle upon Tyne, NE1 7RU, United Kingdom.
Christie
Graham R
GR
Phillips
Siôn R
SR
Russi
Rachel M
RM
Küry
Sébastien
S
Mathers
John C
JC
Taylor
Peter M
PM
Ford
Dianne
D
D000169:Acrodermatitis / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D018938:Caco-2 Cells; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D027682:Cation Transport Proteins; D002412:Cations; D002462:Cell Membrane / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D020895:Enterocytes / Q000378:metabolism*; D005091:Exons; D020224:Expressed Sequence Tags; D017353:Gene Deletion; D006801:Humans; D006863:Hydrogen-Ion Concentration; D026901:Membrane Transport Proteins; D051379:Mice; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D012337:RNA, Ribosomal, 18S / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014158:Transcription, Genetic; D014162:Transfection; D014982:Xenopus laevis; D015032:Zinc / Q000378:metabolism*
D002352:Carrier Proteins; D027682:Cation Transport Proteins; D002412:Cations; D018076:DNA, Complementary; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; D012337:RNA, Ribosomal, 18S; C457225:SLC30A5 protein, human; C486753:Slc30a5 protein, mouse; D004247:DNA; D015032:Zinc