NCBI Summary:
Zinc is an essential cofactor for hundreds of enzymes. It is involved in protein, nucleic acid, carbohydrate, and lipid metabolism, as well as in the control of gene transcription, growth, development, and differentiation. SLC39A6 belongs to a subfamily of proteins that show structural characteristics of zinc transporters (Taylor and Nicholson, 2003 [PubMed 12659941]).[supplied by OMIM, Mar 2008]
General function
Channel/transport protein
Comment
Cellular localization
Plasma membrane
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Ovarian function
Oocyte maturation
Comment
Maternally-derived zinc transporters ZIP6 and ZIP10 drive the mammalian oocyte-to-egg transition. Kong BY 2014 et al.
Rapid cellular zinc influx regulates early mammalian development during the oocyte-to-egg transition through modulation of the meiotic cell cycle. Despite the physiological necessity of this zinc influx, the molecular mechanisms that govern such accumulation are unknown. Here we show that the fully-grown mammalian oocyte does not employ a transcriptionally-based mechanism of zinc regulation involving metal response element-binding transcription factor-1 (MTF-1), as demonstrated by a lack of MTF-1 responsiveness to environmental zinc manipulation. Instead, the mammalian oocyte controls zinc uptake through two maternally-derived and cortically-distributed zinc transporters, ZIP6 and ZIP10. Targeted disruption of these transporters using several approaches during meiotic maturation perturbs the intracellular zinc quota and results in a cell cycle arrest at a telophase I-like state. This arrest phenocopies established models of zinc insufficiency during the oocyte-to-egg transition, indicating the essential function of these maternally expressed transporters. Labile zinc localizes to punctate cytoplasmic structures in the human oocyte, and ZIP6 and ZIP10 are enriched in the cortex. Altogether, we demonstrate a mechanism of metal regulation required for female gamete development that may be evolutionarily conserved.
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Expression regulated by
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Ovarian localization
Oocyte
Comment
Oocyte-cumulus cell interactions regulate free intracellular zinc in mouse oocytes. Lisle RS et al. Zinc increases in the oocyte during maturation and is required for progression and completion of meiosis. The objective of this study was to determine whether cumulus cells regulate the levels of free intracellular zinc in the oocyte during maturation. In the cumulus-oocyte complex (COC), the relative level of free intracellular zinc was almost 4-fold higher in cumulus cells compared to the resident germinal vesicle (GV) stage oocyte. Removal of cumulus cells caused a 4-fold increase in intracellular zinc in the oocyte by one hour after cumulus cell removal, but subsequent co-culture of denuded oocytes with COC decreased free intracellular zinc in the oocyte by 65%. Thus, cumulus cells suppress free intracellular zinc in the oocyte. The zinc transporter proteins Zip6, Zip8, Zip9, Zip10, Zip12, Znt2, Znt4, Znt5 and Znt8 mRNA was higher in oocytes, while Zip1, Zip7, Zip13, Zip14, Znt6, Znt7 and Znt9 mRNA was higher in cumulus cells. Thus a complex zinc transport network is present in the COC. Pretreatment with EGF for 4 hours abolished the ability of cumulus-oocyte complexes to restrict free intracellular zinc in denuded oocytes. Co-culture of denuded MII oocytes with COC lowers free intracellular zinc in mature oocytes. Oocytes matured in vivo or oocytes from older mice had lower levels of free intracellular zinc than oocytes matured in vitro or from younger mice. Thus, a precise mechanism for regulating oocyte zinc homeostasis has been uncovered in the cumulus-oocyte complex that is disrupted with increasing age or by removal of cumulus cells.