Abstract
Magnesium (Mg(2+)) is the second most abundant cation in cells, yet relatively few mechanisms have been identified that regulate cellular levels of this ion. The most clearly identified Mg(2+) transporters are in bacteria and yeast. Here, we use a yeast complementary screen to identify two mammalian genes, MagT1 and TUSC3, as major mechanisms of Mg(2+) influx. MagT1 is universally expressed in all human tissues and its expression level is up-regulated in low extracellular Mg(2+). Knockdown of either MagT1 or TUSC3 protein significantly lowers the total and free intracellular Mg(2+) concentrations in mammalian cell lines. Morpholino knockdown of MagT1 and TUSC3 protein expression in zebrafish embryos results in early developmental arrest; excess Mg(2+) or supplementation with mammalian mRNAs can rescue the effects. We conclude that MagT1 and TUSC3 are indispensable members of the vertebrate plasma membrane Mg(2+) transport system.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Genetically Modified
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Base Sequence
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Cation Transport Proteins / antagonists & inhibitors
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Cation Transport Proteins / chemistry
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Cation Transport Proteins / genetics
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Cation Transport Proteins / metabolism*
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Cell Line
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Embryonic Development / genetics
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Embryonic Development / physiology*
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Female
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Genetic Complementation Test
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Humans
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Ion Transport
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Jurkat Cells
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Magnesium / metabolism*
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Male
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Membrane Proteins / antagonists & inhibitors
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Oligodeoxyribonucleotides, Antisense / genetics
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Pregnancy
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Protein Structure, Secondary
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / growth & development
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Saccharomyces cerevisiae / metabolism
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Saccharomyces cerevisiae Proteins / genetics
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Saccharomyces cerevisiae Proteins / metabolism
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Tissue Distribution
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Tumor Suppressor Proteins / antagonists & inhibitors
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism*
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Zebrafish / embryology
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Zebrafish / genetics
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Zebrafish / metabolism
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Zebrafish Proteins / antagonists & inhibitors
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Zebrafish Proteins / genetics
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Zebrafish Proteins / metabolism
Substances
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ALR1 protein, S cerevisiae
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Cation Transport Proteins
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MagT1 protein, human
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Membrane Proteins
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Oligodeoxyribonucleotides, Antisense
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RNA, Messenger
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Recombinant Proteins
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Saccharomyces cerevisiae Proteins
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TUSC3 protein, human
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Tumor Suppressor Proteins
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Zebrafish Proteins
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Magnesium