Disease relevance of Slc30a1

• 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 [1].

High impact information on Slc30a1

• 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% [2].
• 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 [1].
• In this study, the interplay between zinc binding by MT and its efflux by zinc transporter 1 (ZnT1) was examined genetically [3].
• Only two, ZnT1 and ZnT2 (both cellular Zn exporters), show a progressive down-regulation under Zn-depleted conditions [4].
• In Zn-adequate mice, ZnT1 is diffusely distributed in acinar cell cytoplasm and colocalizes with alpha-amylase but is not detected in pancreatic islets [4].

Chemical compound and disease context of Slc30a1

• Among them, ZnT-1 has been suggested to play a key role in reducing cellular Zn(2+) toxicity [5].

Biological context of Slc30a1

• Changes in ZnT1 gene expression in these experiments paralleled those of metallothionein I (MT-I) [6].
• Inactivation of the Znt1 gene in baby hamster kidney (BHK) cells that do not express their Mt genes results in a zinc-sensitive phenotype and a high level of "free" zinc [3].
• Mouse zinc transporter 1 gene provides an essential function during early embryonic development [7].
• These studies suggest that Znt1 serves an essential function of transporting maternal zinc into the embryonic environment during the egg cylinder stage of development, and further suggest that Znt1 plays a role in zinc homeostasis in adult mice [7].
• The specific expression of ZnT-1 in the Sertoli cells, moreover, is consistent with their role in maintaining a nurturing, closely regulated environment for spermatogenesis [8].

Anatomical context of Slc30a1

• Zinc or cadmium treatment of cell lines rapidly (3 h) and dramatically (about 12-fold) induced ZnT1 mRNA levels [6].
• To address this issue, mice with targeted knockout of the Znt1 gene were generated by homologous recombination in embryonic stem cells [7].
• Expression of the Znt1 gene was detected predominantly in trophoblasts and in the maternal deciduum during the postimplantation period (d5 to d8) [7].
• We have assessed the distribution of the zinc-regulating proteins ZnT-1 and metallothionein I/II (MT I/II) in the mouse seminiferous tubule [8].
• Zinc-regulating proteins, ZnT-1, and metallothionein I/II are present in different cell populations in the mouse testis [8].

Associations of Slc30a1 with chemical compounds

• In cells incubated in medium supplemented with Chelex-treated fetal bovine serum, to remove metal ions, levels of ZnT1 mRNA were reduced, and induction of this message in response to zinc or cadmium was accentuated (up to 31-fold induction) [6].
• Unlike activation of phase II genes by tBHQ, induction of Mt1 expression does not occur in the presence of EDTA, when cells are cultured in zinc-depleted medium, or in cells with reduced intracellular 'free' zinc due to overexpression of ZnT1, a zinc-efflux transporter, indicating that induction requires zinc [9].
• Co-labeling for ZnT-1 and MT I/II demonstrated unique patterns of distribution for these proteins, with ZnT-1 present in Sertoli cells in addition to luminal spermatozoa and MT I/II restricted to spermatocytes [8].
• The present study has investigated the effect of DEHP exposure on several key genes in zinc metabolism (MT-I, MT-II, ZnT-1) for early mouse embryos exposed in utero [10].
• The distribution of ZnT-1 was compared to that of chelatable Zn(2+), visualized by means of neoTimm histochemistry or N-(6-methoxy-8-quinolyl)-p-toluene-sulfonamide (TSQ) histofluorescence [5].

Other interactions of Slc30a1

• Inhibition of RNA synthesis blocked metal induction of ZnT1 and MT-I mRNAs, whereas inhibition of protein synthesis did not [6].
• The transcription factor MTF-1 mediates metal regulation of the mouse ZnT1 gene [6].
• In vivo, ZnT1 mRNA was abundant in the midgestation visceral yolk sac and placenta [6].
• Zinc transporters assessed included both zinc importer (Zip1) and zinc exporters (ZnT1, ZnT2 and ZnT4) [11].
• These findings were confirmed by dual-label immunofluorescence for ZnT-1 and the Sertoli cell marker, vimentin, and by immunoelectron microscopy [8].

Analytical, diagnostic and therapeutic context of Slc30a1

• Immunocytochemistry with an antibody to a myc epitope added to the C-terminus of ZnT-1 revealed localization to the plasma membrane [1].
• Analysis of various metal transporters by bDNA signal amplification assay revealed that the ZnT-1 transporter gene, which encodes for a membrane protein associated with zinc efflux, was expressed three-fold more in CA treated cells than control [12].
• In TR-TBT cells, ZnT1, ZnT3 and ZnT4 were detected by RT-PCR analysis [13].

References