Disruption of TRPM6/TRPM7 complex formation by a mutation in the <i>TRPM6</i> gene causes hypomagnesemia with secondary hypocalcemia

• Vladimir Chubanov

  Institute for Pharmacology and Toxicology, Philipps University Marburg, 35033 Marburg, Germany; University Children's Hospital, Philipps University Marburg, 35037 Marburg, Germany; and Department of Physiology I, University of Regensburg, 93040 Regensburg, Germany

• Siegfried Waldegger

  Institute for Pharmacology and Toxicology, Philipps University Marburg, 35033 Marburg, Germany; University Children's Hospital, Philipps University Marburg, 35037 Marburg, Germany; and Department of Physiology I, University of Regensburg, 93040 Regensburg, Germany

• Michael Mederos y Schnitzler

  Institute for Pharmacology and Toxicology, Philipps University Marburg, 35033 Marburg, Germany; University Children's Hospital, Philipps University Marburg, 35037 Marburg, Germany; and Department of Physiology I, University of Regensburg, 93040 Regensburg, Germany

• Helga Vitzthum

  Institute for Pharmacology and Toxicology, Philipps University Marburg, 35033 Marburg, Germany; University Children's Hospital, Philipps University Marburg, 35037 Marburg, Germany; and Department of Physiology I, University of Regensburg, 93040 Regensburg, Germany

• Martin C. Sassen

  Institute for Pharmacology and Toxicology, Philipps University Marburg, 35033 Marburg, Germany; University Children's Hospital, Philipps University Marburg, 35037 Marburg, Germany; and Department of Physiology I, University of Regensburg, 93040 Regensburg, Germany

• Hannsjörg W. Seyberth

  Institute for Pharmacology and Toxicology, Philipps University Marburg, 35033 Marburg, Germany; University Children's Hospital, Philipps University Marburg, 35037 Marburg, Germany; and Department of Physiology I, University of Regensburg, 93040 Regensburg, Germany

• Martin Konrad

  Institute for Pharmacology and Toxicology, Philipps University Marburg, 35033 Marburg, Germany; University Children's Hospital, Philipps University Marburg, 35037 Marburg, Germany; and Department of Physiology I, University of Regensburg, 93040 Regensburg, Germany

• Thomas Gudermann

  Institute for Pharmacology and Toxicology, Philipps University Marburg, 35033 Marburg, Germany; University Children's Hospital, Philipps University Marburg, 35037 Marburg, Germany; and Department of Physiology I, University of Regensburg, 93040 Regensburg, Germany

抄録

Impaired magnesium reabsorption in patients with TRPM6 gene mutations stresses an important role of TRPM6 (melastatin-related TRP cation channel) in epithelial magnesium transport. While attempting to isolate full-length TRPM6, we found that the human TRPM6 gene encodes multiple mRNA isoforms. Full-length TRPM6 variants failed to form functional channel complexes because they were retained intracellularly on heterologous expression in HEK 293 cells and Xenopus oocytes. However, TRPM6 specifically interacted with its closest homolog, the Mg 2+ -permeable cation channel TRPM7, resulting in the assembly of functional TRPM6/TRPM7 complexes at the cell surface. The naturally occurring S141L TRPM6 missense mutation abrogated the oligomeric assembly of TRPM6, thus providing a cell biological explanation for the human disease. Together, our data suggest an important contribution of TRPM6/TRPM7 heterooligomerization for the biological role of TRPM6 in epithelial magnesium absorption.

収録刊行物

• Proceedings of the National Academy of Sciences

  Proceedings of the National Academy of Sciences 101 (9), 2894-2899, 2004-02-19

  Proceedings of the National Academy of Sciences

キーワード

• Multidisciplinary

詳細情報

• CRID: 1361981469297926144
• NII論文ID: 30016239476
• DOI: 10.1073/pnas.0305252101
• ISSN: 10916490
• ISSN: 00278424
• Web Site: https://pnas.org/doi/pdf/10.1073/pnas.0305252101
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