Mammalian MagT1 and TUSC3 Are Required for Cellular Magnesium Uptake and Vertebrate Embryonic Development

Proc Natl Acad Sci U S A. 2009 Sep 15;106(37):15750-5. doi: 10.1073/pnas.0908332106. Epub 2009 Aug 26.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Base Sequence
  • Cation Transport Proteins / antagonists & inhibitors
  • Cation Transport Proteins / chemistry
  • Cation Transport Proteins / genetics
  • Cation Transport Proteins / metabolism*
  • Cell Line
  • Embryonic Development / genetics
  • Embryonic Development / physiology*
  • Female
  • Genetic Complementation Test
  • Humans
  • Ion Transport
  • Jurkat Cells
  • Magnesium / metabolism*
  • Male
  • Membrane Proteins / antagonists & inhibitors
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Oligodeoxyribonucleotides, Antisense / genetics
  • Pregnancy
  • Protein Structure, Secondary
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Tissue Distribution
  • Tumor Suppressor Proteins / antagonists & inhibitors
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*
  • Zebrafish / embryology
  • Zebrafish / genetics
  • Zebrafish / metabolism
  • Zebrafish Proteins / antagonists & inhibitors
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism

Substances

  • ALR1 protein, S cerevisiae
  • Cation Transport Proteins
  • MagT1 protein, human
  • Membrane Proteins
  • N33 protein, human
  • Oligodeoxyribonucleotides, Antisense
  • RNA, Messenger
  • Recombinant Proteins
  • Saccharomyces cerevisiae Proteins
  • Tumor Suppressor Proteins
  • Zebrafish Proteins
  • Magnesium