The Emerging Role of TRPM7 in the Regulation of Magnesium Homeostasis

TRPM7 and its closely related protein TRPM6 are unique bifunctional molecules consisting of a kinase domain fused to an ion channel. The ion channel belongs to the transient receptor potential (TRP) family of ion channels, TRPM subfamily, while the kinase domain belongs to a family of atypical protein kinases called alpha kinases that are known to phosphorylate substrates within alpha helices. Recent evidence �suggests that TRPM6 and TRPM7 are involved in the regulation of cellular and whole body Mg²⁺ balance. Mutations in human TRPM6 were found to cause hypomagnesemia. Deficiency in TRPM7 inhibits cell proliferation, and this growth defect can be rescued by supplementation with high concentrations of Mg²⁺ . In this review, we discuss the role of TRPM6 and TRPM7 in the regulation of Mg²⁺ homeostasis. We present evidence that TRPM7 is involved in the regulation of Mg²⁺ influx into proliferating cells, while the TRPM7–TRPM6 complex is involved in the regulation of whole body Mg²⁺ balance.