Mammalian MagT1 and TUSC3 are required for cellular magnesium uptake and vertebrate embryonic development.
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.
Zhou
Hao
H
Department of Cardiology, Howard Hughes Medical Institute, Manton Center for Orphan Disease, Children's Hospital Boston, and Harvard Medical School, 1309 Enders, 320 Longwood Avenue, Boston, MA 02115, USA.
Clapham
David E
DE
D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D027682:Cation Transport Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D047108:Embryonic Development / Q000235:genetics / Q000502:physiology*; D005260:Female; D005816:Genetic Complementation Test; D006801:Humans; D017136:Ion Transport; D019169:Jurkat Cells; D008274:Magnesium / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics; D011247:Pregnancy; D017433:Protein Structure, Secondary; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
C110206:ALR1 protein, S cerevisiae; D027682:Cation Transport Proteins; C509698:MagT1 protein, human; D008565:Membrane Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; C524338:TUSC3 protein, human; D025521:Tumor Suppressor Proteins; D029961:Zebrafish Proteins; D008274:Magnesium