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ZnT‐2, a mammalian protein that confers resistance to zinc by facilitating vesicular sequestration.
Author(s) -
Palmiter R. D.,
Cole T. B.,
Findley S. D.
Publication year - 1996
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1996.tb00527.x
Subject(s) - biology , zinc , intracellular , biochemistry , amino acid , complementary dna , endosome , vesicle , open reading frame , microbiology and biotechnology , transport protein , peptide sequence , membrane , gene , chemistry , organic chemistry
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.