Functional characterization of a novel mammalian zinc transporter, ZnT6.
We describe ZnT6, a new member of the CDF (cation diffusion facilitator) family of heavy metal transporters. The human ZNT6 gene was mapped at 2p21-22, while the mouse Znt6 was localized to chromosome 17. Overexpression of ZnT6 in both wild-type yeast and mutants that are deficient in cytoplasmic zinc causes growth inhibition, but this inhibition is abolished in mutant cells with high cytoplasmic zinc. ZnT6 may function in transporting the cytoplasmic zinc into the Golgi apparatus as well as the vesicular compartment, as evidenced by its overlapping intracellular localization with TGN38 and transferrin receptor in the normal rat kidney cells. We also demonstrate that the intracellular distributions of ZnT6 as well as ZnT4 are regulated by zinc in the normal rat kidney cells. The results from this report, combined with those from other studies, suggest that the intracellular zinc homeostasis is mediated by many ZnT proteins, which act in tissue-, cell-, and organelle-specific manners.
Huang
Liping
L
Western Human Nutrition Research Center/Agriculture Research Service/United States Department of Agriculture and the Department of Nutrition and the Rowe Program in Genetics, University of California, Davis, California 95616, USA. lhuang@whnrc.usda.gov
Kirschke
Catherine P
CP
Gitschier
Jane
J
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002478:Cells, Cultured; D002889:Chromosomes, Human, Pair 2; D006224:Cricetinae; D003593:Cytoplasm / Q000378:metabolism; D006023:Glycoproteins; D006056:Golgi Apparatus / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000235:genetics / Q000502:physiology*; D051381:Rats; D011990:Receptors, Transferrin / Q000378:metabolism; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D015032:Zinc / Q000378:metabolism*
D006023:Glycoproteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009414:Nerve Growth Factors; D011990:Receptors, Transferrin; C072237:TGOLN2 protein, human; C513047:Tgoln1 protein, mouse; C513046:Tgoln2 protein, mouse; C513045:Tgoln2 protein, rat; C075936:neurotrophin 6; D015032:Zinc