• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of embojLink to Publisher's site
EMBO J. Apr 15, 1996; 15(8): 1784–1791.
PMCID: PMC450094

ZnT-2, a mammalian protein that confers resistance to zinc by facilitating vesicular sequestration.

Abstract

A cDNA encoding a second zinc transporter (ZnT-2) was isolated from a rat kidney cDNA expression library by complementation of a zinc-sensitive BHK cell line. The protein predicted from the open reading frame of ZnT-2 cDNA has 359 amino acids and initiates with a CTG codon. It resembles ZnT-1 (a plasma membrane protein that stimulates zinc efflux) in overall topology in that it has six membrane-spanning domains, a histidine-rich intracellular loop and a long C-terminal tail; however, the overall amino acid identity is only 26%. Unlike ZnT-1, which is in the plasma membrane and lowers cellular zinc by stimulating zinc efflux, ZnT-2 is localized on vesicles and allows the zinc-sensitive BHK cells to accumulate zinc to levels that are much higher than non-transformed cells can tolerate. Zinc was visualized within these vesicles with zinquin, a zinc-specific fluorescent probe. The intracellular compartment that accumulates zinc is acidic as revealed by staining with acridine orange or LysoTracker. Prolonged exposure of cells expressing ZnT-2 to zinc causes an accretion of intracellular vesicles. We suggest that ZnT-2 protects these cells from zinc toxicity by facilitating zinc transport into an endosomal/lysosomal compartment.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (2.0M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Conklin DS, McMaster JA, Culbertson MR, Kung C. COT1, a gene involved in cobalt accumulation in Saccharomyces cerevisiae. Mol Cell Biol. 1992 Sep;12(9):3678–3688. [PMC free article] [PubMed]
  • Conklin DS, Culbertson MR, Kung C. Interactions between gene products involved in divalent cation transport in Saccharomyces cerevisiae. Mol Gen Genet. 1994 Aug 2;244(3):303–311. [PubMed]
  • Danscher G. Histochemical demonstration of heavy metals. A revised version of the sulphide silver method suitable for both light and electronmicroscopy. Histochemistry. 1981;71(1):1–16. [PubMed]
  • Frederickson CJ, Moncrieff DW. Zinc-containing neurons. Biol Signals. 1994 May-Jun;3(3):127–139. [PubMed]
  • Heim R, Cubitt AB, Tsien RY. Improved green fluorescence. Nature. 1995 Feb 23;373(6516):663–664. [PubMed]
  • Kamizono A, Nishizawa M, Teranishi Y, Murata K, Kimura A. Identification of a gene conferring resistance to zinc and cadmium ions in the yeast Saccharomyces cerevisiae. Mol Gen Genet. 1989 Oct;219(1-2):161–167. [PubMed]
  • Kiefer P, Acland P, Pappin D, Peters G, Dickson C. Competition between nuclear localization and secretory signals determines the subcellular fate of a single CUG-initiated form of FGF3. EMBO J. 1994 Sep 1;13(17):4126–4136. [PMC free article] [PubMed]
  • Nies DH. CzcR and CzcD, gene products affecting regulation of resistance to cobalt, zinc, and cadmium (czc system) in Alcaligenes eutrophus. J Bacteriol. 1992 Dec;174(24):8102–8110. [PMC free article] [PubMed]
  • Nies DH, Nies A, Chu L, Silver S. Expression and nucleotide sequence of a plasmid-determined divalent cation efflux system from Alcaligenes eutrophus. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7351–7355. [PMC free article] [PubMed]
  • Palmiter RD. Regulation of metallothionein genes by heavy metals appears to be mediated by a zinc-sensitive inhibitor that interacts with a constitutively active transcription factor, MTF-1. Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1219–1223. [PMC free article] [PubMed]
  • Palmiter RD. Constitutive expression of metallothionein-III (MT-III), but not MT-I, inhibits growth when cells become zinc deficient. Toxicol Appl Pharmacol. 1995 Nov;135(1):139–146. [PubMed]
  • Palmiter RD, Findley SD. Cloning and functional characterization of a mammalian zinc transporter that confers resistance to zinc. EMBO J. 1995 Feb 15;14(4):639–649. [PMC free article] [PubMed]
  • Rowe LB, Nadeau JH, Turner R, Frankel WN, Letts VA, Eppig JT, Ko MS, Thurston SJ, Birkenmeier EH. Maps from two interspecific backcross DNA panels available as a community genetic mapping resource. Mamm Genome. 1994 May;5(5):253–274. [PubMed]
  • von Heijne G. Membrane proteins: from sequence to structure. Annu Rev Biophys Biomol Struct. 1994;23:167–192. [PubMed]
  • Yoshimori T, Yamamoto A, Moriyama Y, Futai M, Tashiro Y. Bafilomycin A1, a specific inhibitor of vacuolar-type H(+)-ATPase, inhibits acidification and protein degradation in lysosomes of cultured cells. J Biol Chem. 1991 Sep 15;266(26):17707–17712. [PubMed]
  • Zalewski PD, Forbes IJ, Betts WH. Correlation of apoptosis with change in intracellular labile Zn(II) using zinquin [(2-methyl-8-p-toluenesulphonamido-6-quinolyloxy)acetic acid], a new specific fluorescent probe for Zn(II). Biochem J. 1993 Dec 1;296(Pt 2):403–408. [PMC free article] [PubMed]
  • Zalewski PD, Millard SH, Forbes IJ, Kapaniris O, Slavotinek A, Betts WH, Ward AD, Lincoln SF, Mahadevan I. Video image analysis of labile zinc in viable pancreatic islet cells using a specific fluorescent probe for zinc. J Histochem Cytochem. 1994 Jul;42(7):877–884. [PubMed]

Articles from The EMBO Journal are provided here courtesy of The European Molecular Biology Organization

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Compound
    Compound
    PubChem Compound links
  • Gene
    Gene
    Gene links
  • Gene (nucleotide)
    Gene (nucleotide)
    Records in Gene identified from shared sequence links
  • GEO Profiles
    GEO Profiles
    Related GEO records
  • HomoloGene
    HomoloGene
    HomoloGene links
  • MedGen
    MedGen
    Related information in MedGen
  • Nucleotide
    Nucleotide
    Published Nucleotide sequences
  • OMIM
    OMIM
    OMIM record citing PubMed
  • Pathways + GO
    Pathways + GO
    Pathways, annotations and biological systems (BioSystems) that cite the current article.
  • Protein
    Protein
    Published protein sequences
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...