ZnT-2, a mammalian protein that confers resistance to zinc by facilitating vesicular sequestration.
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.
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Howard Hughes Medical Institute, University of Washington, Seattle 98195-7370, USA.
Cole
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Findley
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001693:Biological Transport, Active; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D027682:Cation Transport Proteins; D002460:Cell Line; D002874:Chromosome Mapping; D006224:Cricetinae; D018076:DNA, Complementary / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009115:Muridae; D009154:Mutation; D051381:Rats; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions / Q000378:metabolism; D014162:Transfection; D015032:Zinc / Q000378:metabolism* / Q000633:toxicity
D002352:Carrier Proteins; D027682:Cation Transport Proteins; D018076:DNA, Complementary; D008565:Membrane Proteins; C485803:Slc30a1 protein, mouse; C099189:Slc30a2 protein, rat; C092392:Slc30a1 protein, rat; D015032:Zinc