Mammalian MagT1 and TUSC3 are required for cellular magnesium uptake and vertebrate embryonic development
- Department of Cardiology, Howard Hughes Medical Institute, Manton Center for Orphan Disease, Children's Hospital Boston, and Department of Neurobiology, Harvard Medical School, 1309 Enders, 320 Longwood Avenue, Boston, MA 02115
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Contributed by David E. Clapham, July 26, 2009
Abstract
Magnesium (Mg2+) 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 Mg2+ 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 Mg2+ influx. MagT1 is universally expressed in all human tissues and its expression level is up-regulated in low extracellular Mg2+. Knockdown of either MagT1 or TUSC3 protein significantly lowers the total and free intracellular Mg2+ concentrations in mammalian cell lines. Morpholino knockdown of MagT1 and TUSC3 protein expression in zebrafish embryos results in early developmental arrest; excess Mg2+ or supplementation with mammalian mRNAs can rescue the effects. We conclude that MagT1 and TUSC3 are indispensable members of the vertebrate plasma membrane Mg2+ transport system.
Footnotes
- 1To whom correspondence should be addressed. E-mail: dclapham{at}enders.tch.harvard.edu
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Author contributions: H.Z. and D.E.C. designed research; H.Z. performed research; H.Z. contributed new reagents/analytic tools; H.Z. and D.E.C. analyzed data; and H.Z. and D.E.C. wrote the paper.
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The authors declare no conflict of interest.
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This article contains supporting information online at www.pnas.org/cgi/content/full/0908332106/DCSupplemental.
