title: The B. subtilis MgtE magnesium transporter can functionally compensate TRPM7-deficiency in vertebrate B-cells.
abstract: Recent studies have shown that the vertebrate magnesium transporters Solute carrier family 41, members 1 and 2 (SLC41A1, SLC41A2) and Magnesium transporter subtype 1 (MagT1) can endow vertebrate B-cells lacking the ion-channel kinase Transient receptor potential cation channel, subfamily M, member 7 (TRPM7) with a capacity to grow and proliferate. SLC41A1 and SLC41A2 display distant homology to the prokaryotic family of Mg(2+) transporters, MgtE, first characterized in Bacillus subtilis. These sequence similarities prompted us to investigate whether MgtE could potentially compensate for the lack of TRPM7 in the vertebrate TRPM7-deficient DT40 B-cell model system. Here, we report that overexpression of MgtE is able to rescue the growth of TRPM7-KO DT40 B-cells. However, contrary to a previous report that describes regulation of MgtE channel gating by Mg(2+) in a bacterial spheroplast model system, whole cell patch clamp analysis revealed no detectable current development in TRPM7-deficient cells expressing MgtE. In addition, we observed that MgtE expression is strongly downregulated at high magnesium concentrations, similar to what has been described for its vertebrate homolog, SLC41A1. We also show that the N-terminal cytoplasmic domain of MgtE is required for normal MgtE channel function, functionally confirming the predicted importance of this domain in regulation of MgtE-mediated Mg(2+) entry. Overall, our findings show that consistent with its proposed function, Mg(2+) uptake mediated by MgtE is able to restore cell growth and proliferation of TRPM7-deficient cells and supports the concept of functional homology between MgtE and its vertebrate homologs.
authors.affiliation: Seattle Children's Research Institute, Seattle, Washington, United States of America.
authors.forename: Jaya
authors.initials: J
authors.lastname: Sahni
authors.forename: Yumei
authors.initials: Y
authors.lastname: Song
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Scharenberg
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017920:Antiporters / Q000737:chemistry / Q000502:physiology*; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D001412:Bacillus subtilis / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000502:physiology*; D027682:Cation Transport Proteins / Q000737:chemistry; D002455:Cell Division; D002460:Cell Line; D002645:Chickens; D006801:Humans; D008274:Magnesium / Q000378:metabolism; D008969:Molecular Sequence Data; D018408:Patch-Clamp Techniques; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D050053:TRPM Cation Channels / Q000378:metabolism*
chemical_list: D017920:Antiporters; D001426:Bacterial Proteins; D027682:Cation Transport Proteins; C092192:MgtE protein, bacteria; D050053:TRPM Cation Channels; D008274:Magnesium