Essential role for TRPM6 in epithelial magnesium transport and body magnesium homeostasis.
Magnesium is an important cofactor for many biological processes such as protein synthesis, nucleic acid stability and neuromuscular excitability. The extracellular magnesium concentration is regulated tightly by the extent of intestinal absorption and renal excretion. Despite their critical role in magnesium handling, the molecular mechanisms mediating transepithelial transport are still not understood completely. Recently, genetic studies in patients with primary hypomagnesaemia and secondary hypocalcaemia (HSH), a combined defect of intestinal magnesium absorption and renal magnesium conservation, have identified "transient receptor potential (melastatin) 6" (TRPM6) as the first component involved directly in epithelial magnesium reabsorption. TRPM7, the closest homologue of TRPM6, has a central role in Mg(2+) uptake in vertebrate cells since TRPM7-deficient cells become Mg(2+) deficient and are not viable. TRPM7 has been characterized functionally as a constitutively active ion channel permeable for a variety of cations including calcium and magnesium and regulated by intracellular concentrations of magnesium and/or magnesium-nucleotide complexes. Both proteins share the unique feature of cation channels fused to serine/threonine kinase domains. This review summarizes recent data that has emerged from molecular genetic, biochemical and electrophysiological studies on these fascinating two new proteins and their involvement in epithelial magnesium transport.
Chubanov
Vladimir
V
Institute of Pharmacology and Toxicology, Philipps-University, Marburg, Germany.
Gudermann
Thomas
T
Schlingmann
Karl P
KP
D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D006996:Hypocalcemia / Q000097:blood / Q000209:etiology; D008274:Magnesium / Q000378:metabolism*; D008275:Magnesium Deficiency / Q000097:blood; D017346:Protein Serine-Threonine Kinases; D050053:TRPM Cation Channels / Q000502:physiology*
D050053:TRPM Cation Channels; C459082:TRPM6 protein, human; D017346:Protein Serine-Threonine Kinases; C486583:TRPM7 protein, human; D008274:Magnesium