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Intestinal and placental zinc transport pathways

Published online by Cambridge University Press:  07 March 2007

Dianne Ford
Dianne Ford*
Affiliation:
School of Cell and Molecular Biosciences, Agriculture Building, University of Newcastle, Kings Road, Newcastle upon Tyne NE1 7RU, UK
*
Corresponding author: Dr Dianne Ford, fax +44 191 2228684, email [email protected]
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Abstract

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Mammalian members of the cation diffusion facilitator (CDF) and zrt-, irt-like protein (ZIP) families of Zn transporters, initially identified in Saccharomyces cerevisiae and Arabidopsis thalania spp., have been cloned during the last 8 years and have been classified as families SLC30 and SLC39 respectively. The cloning of human Zn transporters ZnT-like transporter 1 (hZTL1)/ZnT5 (SLC30A5) and hZIP4 (SLC39A4) were major advances in the understanding of the molecular mechanisms of dietary Zn absorption. Both transporters are localised at the enterocyte apical membrane and are, therefore, potentially of fundamental importance in dietary Zn uptake. hZTL1 mediates Zn uptake when expressed in Xenopus laevis oocytes and hZIP4 is mutated in most cases of the inherited Zn deficiency disease acrodermatitis enteropathica. Localisation of hZTL1/ZnT5 at the apical membrane of the placental syncytiotrophoblast indicates a fundamental role in the transfer of Slc30 Zn to the foetus. Observations in rodent models indicate that in the intestine increased Zn availability increases expression of Zn transporters. Human intestinal Caco-2 cells show a similar response to increasing the Zn2+ concentration of the nutrient medium in relation to the expression of mRNA corresponding to several Zn transporters and that of ZnT1 (SLC30A1) and hZTL1/ZnT5 proteins. In the human placental cell line JAR, however, expression at the mRNA level of a number of Zn transporters is not modified by Zn availability, whilst ZnT1 and hZTL1/ZnT5 proteins are reduced under Zn-supplemented conditions. These differences between Caco-2 and JAR cells in Zn transporter gene responses to Zn supply may reflect the different extracellular Zn concentrations encountered by the corresponding cell types in vitro.

Keywords

Dietary zinc absorptionPlacental zinc transportSLC30 transportersSLC39 transporters
Type
Symposium on ‘New insights into the molecular regulation of trace element metabolism’
Information
Proceedings of the Nutrition Society , Volume 63 , Issue 1 , February 2004 , pp. 21 - 29
Copyright
Copyright © The Nutrition Society 2004

References

Aslam, N & McArdle, HJ (1992) Mechanism of zinc uptake by microvilli isolated from human term placenta. Journal of Cell Physiology 151 533–538.CrossRefGoogle ScholarPubMed
Bax, CM & Bloxam, DL (1995) Two major pathways of zinc(II) acquisition by human placental syncytiotrophoblast. Journal of Cell Physiology 164 546–554.CrossRefGoogle ScholarPubMed
Begum, NA, Kobayashi, M, Moriwaki, Y, Matsumoto, M, Toyoshima, K & Seya, T (2002) Mycobacterium bovis BCG cell wall and lipopolysaccharide induce a novel gene, BIGM103, encoding a 7-TM protein: identification of a new protein family having Zn-transporter and Zn-metalloprotease signatures Genomics 80, 630–645.CrossRefGoogle ScholarPubMed
Caulfield, LE, Zavaleta, N, Shankar, AH & Merialdi, M (1998) Potential contribution of maternal zinc supplementation during pregnancy to maternal and child survival American Journal of Clinical Nutrition 68, 499S–508S.CrossRefGoogle ScholarPubMed
Coleman, JE (1992) Zinc proteins: enzymes, storage proteins, transcription factors, and replication proteins, Annual Reviews of Biochemistry 61, 897–946.CrossRefGoogle ScholarPubMed
Condomina, J, Zornoza-Sabina, T, Granero, L & Polache, A (2002) Kinetics of zinc transport in vitro in rat small intestine and colon: interaction with copper European Journal of Pharmaceutical Sciences 16 289–295.CrossRefGoogle ScholarPubMed
Conklin, DS, McMaster, JA, Culbertson, MR & Kung, C (1992) COT1, a gene involved in cobalt accumulation in Saccharomyces cerevisiae Molecular and Cellular Biology 12 3678–3688.Google ScholarPubMed
Cragg, RA, Christie, GR, Phillips, SR, Russi, RM, Kury, S, Mathers, JC, Taylor, PM & Ford, D (2002) A novel zinc-regulated human zinc transporter, hZTL1, is localised to the enterocyte apical membrane. Journal of Biological Chemistry 277, 22789–22797.CrossRefGoogle Scholar
Cragg, RA, Phillips, SR, Mathers, JC & Ford, D (2003) Immunolocalisation of the zinc transporter hZTL1 at the apical membrane of human jejunum and Caco-2 cells. Journal of Physiology 549, C1.Google Scholar
Department of Health (1991) Dietary Reference Values for Food Energy and Nutrients for the United Kingdom. Report in Health and Social Subjects no. 41 London: H.M. Stationery Office.Google Scholar
Dufner-Beattie, J, Wang, F, Kuo, YM Gitschier, J, Eide, D & Andrews, GK (2003) The acrodermatitis enteropathica gene ZIP4 encodes a tissue-specific, zinc-regulated zinc transporter in mice. Journal of Biological Chemistry 278 33474–33481.CrossRefGoogle ScholarPubMed
Eide, DJ (2003) The SLC39 family of metal ion transporters Pflugers Archives – European Journal of Physiology(In the Press).Google ScholarPubMed
Eide, DJ, Broderius, M, Fett, J, Guerinot, ML (1996) A novel iron-regulated metal transporter from plants identified by functional expression in yeast Proceedings of the National Academy of Sciences USA 93 5624–5628.CrossRefGoogle ScholarPubMed
Fleet, JC, Turnbull, AJ, Bourcier, M & Wood, R (1993) Vitamin D-sensitive and quinacrine-sensitive zinc transport in human intestinal cell line Caco-2 American Journal of Physiology 264, G1037–G1045.Google ScholarPubMed
Gaither, LA & Eide, DJ (2000) Functional expression of the human hZIP2 zinc transporter. Journal of Biological Chemistry 275, 5560–5564.CrossRefGoogle ScholarPubMed
Gaither, LA & Eide, DJ (2001a) Eukaryotic zinc transporters and their regulation Biometals 14, 251–270.CrossRefGoogle ScholarPubMed
Gaither, LA & Eide, DJ (2001b) The human ZIP1 transporter mediates zinc uptake in human K562 erythroleukaemia cells. Journal of Biological Chemistry 276, 22258–22264.CrossRefGoogle Scholar
Gisbert-Gonzalez, SL, Torres-Molina, F (1996) Zinc uptake in five sectors of the rat gastrointestinal tract: kinetic study in the whole colon Pharmacological Research 13, 1154–1161.CrossRefGoogle ScholarPubMed
Gitan, RS & Eide, DJ (2000) Zinc-regulated ubiquitin conjugation signals endocytosis of the yeast ZRT1 zinc transporter Biochemical Journal 346, 329–336.CrossRefGoogle ScholarPubMed
Grotz, N, Fox, T, Connolly, E, Park, W, Guerinot, ML & Eide, DJ (1998) Identification of a family of zinc transporter genes from Arabidopsis that respond to zinc deficiency Proceedings of the National Academy of Sciences USA 95, 7220–7224.CrossRefGoogle ScholarPubMed
Gunshin, H, Mackenzie, B, Berger, UV, Gunshin, Y, Romero, MF, Boron, WF, Nussberger, S, Gollan, JL & Hediger, MA (1997) Cloning and characterization of a mammalian proton-coupled metal-ion transporter Nature 388, 482–488.CrossRefGoogle ScholarPubMed
Heuchel, R, Radtke, F, Georgiev, O, Stark, G, Aguet, M, Schaffner, W (1994) The transcription factor MTF-1 is essential for basal and heavy metal-induced metallothionein gene expression EMBO Journal 13, 2870–2875.CrossRefGoogle ScholarPubMed
Hoadley, JE, Leinart, AS & Cousins, RJ (1987) Kinetic analysis of zinc uptake and serosal transfer by vascularly perfused rat intestine American Journal of Physiology 252, G825–G831.Google ScholarPubMed
Hofmann, K & Stoffel, W (1993) TMbase – A database of membrane spanning protein segments Biological Chemistry Hoppe-Seyler 374 166.Google Scholar
Huang, L & Gitschier, J (1997) A novel gene involved in zinc transport is deficient in the lethal milk mouse Nature Genetics 17, 292–297.CrossRefGoogle ScholarPubMed
Huang, L, Kirschke, CP & Gitschier, J (2002) Functional characterisation of a novel mammalian zinc transporter, ZnT6. Journal of Biological Chemistry 277, 26389–26395.CrossRefGoogle ScholarPubMed
Kambe, T, Narita, H, Yamaguchi-Iwai, Y, Hirose, J, Amano, T, Sugiura, N, Sasaki, R, Mori, K, Iwanaga, T & Nagao, M (2002) Cloning and characterization of a novel mammalian zinc transporter, zinc transporter 5, abundantly expressed in pancreatic beta cells. Journal of Biological Chemistry 277, 19049–19055.CrossRefGoogle ScholarPubMed
Kamizono, A, Nishizawa, M, Teranishi, Y, Murata, K & Kimura, A (1989) Identification of a gene conferring resistance to zinc and cadmium ions in the yeast Saccharomyces cerevisiae Molecular and General Genetics 219, 161–167.CrossRefGoogle ScholarPubMed
Kirschke, CP & Huang, L (2003) ZnT7, a novel mammalian zinc transporter accumulates zinc in the Golgi apparatus. Journal of Biological Chemistry 278, 4096–4102.CrossRefGoogle ScholarPubMed
Kury, S, Dreno, B, Bezieau, S, Giraudet, S, Kharfi, M, Kamoun, R & Moisan, JP (2002) Identification of SLC39A4, a gene involved in acrodermatitis enteropathica Nature Genetics 31, 239–240.CrossRefGoogle ScholarPubMed
Langmade, SJ, Ravindra, R, Daniels, PJ & Andrews, GK (2000) The transcription factor MTF-1 mediates metal regulation of the mouse ZnT1 gene. Journal of Biological Chemistry 275, 34803–34809.CrossRefGoogle ScholarPubMed
Lee, HH, Prasad, AS, Brewer, GJ & Owyang, C (1989) Zinc absorption in human small intestine American Journal of Physiology 256, G87–G91.Google ScholarPubMed
Liuzzi, JP, Blanchard, RK & Cousins, RJ (2001) Differential regulation of zinc transporter 1, 2 and 4 mRNA expression by dietary zinc in rats. Journal of Nutrition 131, 46–52.CrossRefGoogle ScholarPubMed
Liuzzi, JP, Bobo, JA, Cui, L, McMahon, RJ & Cousins, RJ (2003) Zinc transporters 1, 2 and 4 are differentially expressed and localized in rats during pregnancy and lactation. Journal of Nutrition 33, 342–351.CrossRefGoogle Scholar
McCall, KA, Huang, C & Fierke, CA (2000) Function and mechanism of zinc metalloenzymes. Journal of Nutrition 130, 1437S–1446S.CrossRefGoogle ScholarPubMed
McMahon, RJ & Cousins, RJ (1998) Regulation of the zinc transporter ZnT-1 by dietary zinc Proceedings of the National Academy of Sciences USA 95, 4841–4846.CrossRefGoogle ScholarPubMed
Menard, MP & Cousins, RJ (1983) Zinc transport by brush border membrane vesicles from rat intestine. Journal of Nutrition 113, 1434–1442.CrossRefGoogle ScholarPubMed
Milon, B, Dhermy, D, Pountney, D, Bourgeois, M & Beaumont, C (2001) Differential subcellular localisation of hZip1 in adherent and non-adherent cells FEBS Letters 507, 241–246.CrossRefGoogle ScholarPubMed
Murgia, C, Vespignani, I, Cerase, J, Nobili, F & Perozzi, G (1999) Cloning, expression and vesicular localisation of zinc transporter Dri 27/ZnT4 in intestinal tissue and cells American Journal of Physiology 277, G1231–G1239.Google ScholarPubMed
Office for National Statistics (2003) The National Diet and Nutrition Survey: Adults Ages 19 to 64 Years. vol. 3. Vitamin and Mineral Intake and Urinary Analytes London: The Stationery Office.Google Scholar
Outten, CE & O'Halloran, TV (2001) Femtomolar sensitivity of metalloregulatory proteins controlling zinc homeostasis Science 292, 2488–2492.CrossRefGoogle ScholarPubMed
Page, KR, Abramovich, DR, Aggett, PJ, Bain, M, Chipperfield, AR, Durdy, H McLachlan, J & Smale, A (1992) Uptake of zinc by human placental microvillus border membranes and characterization of the effects of cadmium on this process Placenta 13, 151–161.CrossRefGoogle ScholarPubMed
Palmiter, RD, Cole, TB & Findley, SD (1996a) ZnT-2, a mammalian protein that confers resistance to zinc by facilitating vesicular sequestration EMBO Journal 15, 1784–1791.CrossRefGoogle ScholarPubMed
Palmiter, RD, Cole, TB, Quaife, CJ & Findley, SD (1996b) ZnT-3, a putative transporter of zinc into synaptic vesicles Proceedings of the National Academy of Sciences USA 93, 14934–14939.CrossRefGoogle ScholarPubMed
Palmiter, RD & Findley, SD (1995) Cloning and functional characterisation of a mammalian zinc transporter that confers resistance to zinc EMBO Journal 14, 639–649.CrossRefGoogle ScholarPubMed
Palmiter, RD & Huang, L (2003) Efflux and compartmentalization of zinc by members of the SLC30 family of solute carriers Pflugers Archives – European Journal of Physiology (In the Press).Google ScholarPubMed
Paulsen, IT & Saier, MH Jr (1997) A novel family of ubiquitous heavy metal ion transport proteins. Journal of Membrane Biology 156, 99–103.CrossRefGoogle ScholarPubMed
Reeves, PG, Briske-Anderson, M & Johnson, L (2001) Pre-treatment of Caco-2 cells with zinc during the differentiation phase alters the kinetics of zinc uptake and transport. Journal of Nutritional Biochemistry 12, 674–684.CrossRefGoogle ScholarPubMed
Rink, L & Gabriel, P (2000) Zinc and the immune system Proceedings of the Nutrition Society 59, 541–552.CrossRefGoogle ScholarPubMed
Rogers, EE, Eide, DJ & Guerinot, ML (1999) Altered cation selectivity in an Arabidopsis metal transporter Proceedings of the National Academy of Sciences USA 97, 12356–12360.CrossRefGoogle Scholar
Seal, CJ & Mathers, JC (1989) Intestinal zinc transfer by everted gut sacs from rats given diets containing different amounts and types of dietary fibre British Journal of Nutrition 62, 151–163.CrossRefGoogle ScholarPubMed
Smith, KT & Cousins, RJ (1980) Quantitative aspects of zinc absorption by isolated, vascularly perfused rat intestine. Journal of Nutrition 110, 316–323.CrossRefGoogle ScholarPubMed
Suzuki, A & Endo, T (2002) Ermelin, an endoplasmic reticulum transmembrane protein, contains the novel HELP domain conserved in eukaryotes Gene 284, 31–40.CrossRefGoogle ScholarPubMed
Tacnet, F, Watkins, DW & Ripoche, P (1990) Studies of zinc transport into brush-border membrane vesicles isolated from pig small intestine Biochimica et Biophysica Acta 1024, 323–330.CrossRefGoogle ScholarPubMed
Tandy, S, Williams, M, Leggett, A, Lopez-Jimenez, M, Dedes, M, Ramesh, B, Srai, SK & Sharp, P (2000) Nramp2 expression is associated with pH-dependent iron uptake across the apical membrane of human intestinal Caco-2 cells. Journal of Biological Chemistry 275, 1023–1029.CrossRefGoogle ScholarPubMed
Wang, K, Zhou, B, Kuo, YM, Zemansky, J & Gitschier, J (2002) A novel member of a zinc transporter family is defective in acrodermatitis enteropathica American Journal of Human Genetics 71, 66–73.CrossRefGoogle ScholarPubMed
Wood, RJ (2000) Asessment of marginal zinc status in humans. Journal of Nutrition 130, 1350S–1354S.CrossRefGoogle Scholar
Zhao, H & Eide, D (1996a) The yeast ZRT1 gene encodes the zinc transporter of a high affinity uptake system induced by zinc limitation Proceedings of the National Academy of Sciences USA 93, 2454–2458.CrossRefGoogle ScholarPubMed
Zhao, H & Eide, D (1996b) The ZRT2 gene encodes the low affinity zinc transporter in Saccharomyces cerevisiae. Journal of Biological Chemistry 271, 23203–23210.CrossRefGoogle ScholarPubMed