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TRPM6 and TRPM7: A Mul-TRP-PLIK-Cation of Channel Functions

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Unique among ion channels, TRPM6 and TRPM7 garnered much interest upon their discovery as the first ion channels to possess their own kinase domain. Soon after their identification, the two proteins were quickly linked to the regulation of magnesium homeostasis. However, study of their physiological functions in mouse and zebrafish have revealed expanding roles for these channel-kinases that include skeletogenesis and melanopore formation, thymopoiesis, cell adhesion, and neural fold closure during early development. In addition, mutations in the TRPM6 gene constitute the underlying genetic defect in hypomagnesemia with secondary hypocalcemia, a rare autosomal-recessive disease characterized by low serum magnesium accompanied by hypocalcemia. Depletion of TRPM7 expression in brain, on the other hand, proved successful in mitigating much of the cellular devastation that accompanies oxygen-glucose deprivation during ischemia. The aim of this review is to summarize the data emerging from molecular genetic, biochemical, electrophysiological, and pharmacological studies of these unique channel-kinases.

Keywords: 17--estradiol; CHAK1; CHO-K1; CHO-K1 cells; COOH-terminal tails; DT40-KO; Demeuse's measurements; Dictyostelium myosin II heavy chain kinases; GXGXXG; Gly1799; KMG104AM; LTRPC7; Mul-TRP-PLIK-Cation; PKA; TGF-1; TRP-PLIK; TRPM6; TRPM6 cDNA; TRPM7; TRPM7--kinase; Xenopus oocytes; alpha-kinases; autophosphorylation; bradykinin-stimulated Ca2+; cAMP; calcium; cell adhesion; channel; dimerization sequence; elongation factor 2 kinase; hypocalcemia; hypomagnesemia; kidney kinase; kinase; magnesium; magnesium homeostasis; melanoma kinase; melanopore formation; myosin IIA; non-selective channel blocker 2-APB; phospholipase C-1 (PLC1); phosphorylation; protein kinases; pyrimidine-based nucleoside triphosphates; skeletogenesis; small interfering RNA; thymopoiesis; transient receptor potential

Document Type: Research Article

Publication date: 2011-01-01

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  • Current Pharmaceutical Biotechnology aims to cover all the latest and outstanding developments in Pharmaceutical Biotechnology. Each issue of the journal contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics in both pre-clinical and clinical areas of Pharmaceutical Biotechnology. Current Pharmaceutical Biotechnology is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments.
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