| First Author | Palmiter RD | Year | 1995 |
| Journal | EMBO J | Volume | 14 |
| Issue | 4 | Pages | 639-49 |
| PubMed ID | 7882967 | Mgi Jnum | J:23612 |
| Mgi Id | MGI:71195 | Doi | 10.1002/j.1460-2075.1995.tb07042.x |
| Citation | Palmiter RD, et al. (1995) Cloning and functional characterization of a mammalian zinc transporter that confers resistance to zinc. EMBO J 14(4):639-49 |
| abstractText | A cDNA encoding a zinc transporter (ZnT-1) was isolated from a rat kidney cDNA expression library by complementation of a mutated, zinc-sensitive BHK cell line. This cDNA was used to isolate the homologous mouse ZnT-1 gene. The proteins predicted for these transporters contain six membrane-spanning domains, a large intracellular loop and a C-terminal tail. ZnT-1 is homologous to zinc and cobalt resistance genes of yeast. Immunocytochemistry with an antibody to a myc epitope added to the C-terminus of ZnT-1 revealed localization to the plasma membrane. Transformation of normal cells with a mutant ZnT-1 lacking the first membrane-spanning domain conferred zinc sensitivity on wild-type cells, suggesting that ZnT-1 functions as a multimer. Deletion of the first two membrane-spanning domains resulted in a non-functional molecule, whereas deletion of the C-terminal tail produced a toxic phenotype. Mutant cells have a slightly higher steady-state level of intracellular zinc and high basal expression of a zinc-dependent reporter gene compared with normal cells. Mutant cells have a lower turnover of 65Zn compared with normal cells or mutant cells transformed with ZnT-1. We propose that ZnT-1 transports zinc out of cells and that its absence accounts for the increased sensitivity of mutant cells to zinc toxicity. |
