Along with the SLC30 family, SLC39 family members regulate zinc movement in cells. SLC39 metal ion transporters accumulate zinc into the cytosol. Membrane topology modelling suggests the presence of eight TM regions with both termini extracellular or in the lumen of intracellular organelles. The mechanism for zinc transport for many members is unknown but appears to involve co-transport of bicarbonate ions [2,4].

Zinc fluxes may be monitored through the use of radioisotopic Zn-65 or the fluorescent dye FluoZin 3.

The bicarbonate transport inhibitor DIDS has been reported to inhibit cation accumulation through ZIP14 [2].

* Key recommended reading is highlighted with an asterisk

Eide DJ. (2004) The SLC39 family of metal ion transporters. Pflugers Arch, 447 (5): 796-800. [PMID:12748861]

Franz MC, Anderle P, Bürzle M, Suzuki Y, Freeman MR, Hediger MA, Kovacs G. (2013) Zinc transporters in prostate cancer. Mol Aspects Med, 34 (2-3): 735-41. [PMID:23506906]

Himeno S, Yanagiya T, Fujishiro H. (2009) The role of zinc transporters in cadmium and manganese transport in mammalian cells. Biochimie, 91 (10): 1218-22. [PMID:19375483]

* Hojyo S, Fukada T. (2016) Zinc transporters and signaling in physiology and pathogenesis. Arch Biochem Biophys, 611: 43-50. [PMID:27394923]

* Jeong J, Eide DJ. (2013) The SLC39 family of zinc transporters. Mol Aspects Med, 34 (2-3): 612-9. [PMID:23506894]

* Kambe T, Hashimoto A, Fujimoto S. (2014) Current understanding of ZIP and ZnT zinc transporters in human health and diseases. Cell Mol Life Sci, 71 (17): 3281-95. [PMID:24710731]

* Kambe T, Tsuji T, Hashimoto A, Itsumura N. (2015) The Physiological, Biochemical, and Molecular Roles of Zinc Transporters in Zinc Homeostasis and Metabolism. Physiol Rev, 95 (3): 749-784. [PMID:26084690]

* Marger L, Schubert CR, Bertrand D. (2014) Zinc: an underappreciated modulatory factor of brain function. Biochem Pharmacol, 91 (4): 426-35. [PMID:25130547]

Rungby J. (2010) Zinc, zinc transporters and diabetes. Diabetologia, 53 (8): 1549-51. [PMID:20490449]

Thévenod F. (2010) Catch me if you can! Novel aspects of cadmium transport in mammalian cells. Biometals, 23 (5): 857-75. [PMID:20204475]

1. Dalton TP, He L, Wang B, Miller ML, Jin L, Stringer KF, Chang X, Baxter CS, Nebert DW. (2005) Identification of mouse SLC39A8 as the transporter responsible for cadmium-induced toxicity in the testis. Proc Natl Acad Sci USA, 102 (9): 3401-6. [PMID:15722412]

2. Girijashanker K, He L, Soleimani M, Reed JM, Li H, Liu Z, Wang B, Dalton TP, Nebert DW. (2008) Slc39a14 gene encodes ZIP14, a metal/bicarbonate symporter: similarities to the ZIP8 transporter. Mol Pharmacol, 73 (5): 1413-23. [PMID:18270315]

3. Liu Q, Jenkitkasemwong S, Prami TA, McCabe SM, Zhao N, Hojyo S, Fukada T, Knutson MD. (2023) Metal-ion transporter SLC39A8 is required for brain manganese uptake and accumulation. J Biol Chem, 299 (8): 105078. [PMID:37482277]

4. Liu Z, Li H, Soleimani M, Girijashanker K, Reed JM, He L, Dalton TP, Nebert DW. (2008) Cd2+ versus Zn2+ uptake by the ZIP8 HCO3--dependent symporter: kinetics, electrogenicity and trafficking. Biochem Biophys Res Commun, 365 (4): 814-20. [PMID:18037372]

5. Liuzzi JP, Aydemir F, Nam H, Knutson MD, Cousins RJ. (2006) Zip14 (Slc39a14) mediates non-transferrin-bound iron uptake into cells. Proc Natl Acad Sci USA, 103 (37): 13612-7. [PMID:16950869]

Michal Hershfinkel Department of Physiology and Cell Biology Ben Gurion University of the Negev Faculty of Health Sciences Beer-Sheva 84105 Israel