P15 - Role of kinase-coupled TRP channels in Mg2+ homeostasis: From mouse models to human disease
TRPM6 and TRPM7 are bifunctional proteins comprising a TRP channel segment linked to an α-type protein kinase. Mutations in the human TRPM6 gene cause a familial form of hypomagnesemia. Mechanistically, the regulation of Mg2+ homeostasis and the pathophysiology of TRPM6 mutations are poorly understood. This project will address these issues capitalizing on novel mouse models, antibodies, and ligands. Conditional disruption of the Trpm6 gene results in severe Mg2+ depletion and a syndrome resembling premature aging. Thus, the project will grant insight into the role of Mg2+ in physiology and dissect the relationship between an essential nutrient and cell metabolism and aging.
Figure. Interplay of TRPM6 and TRPM7 kinase-coupled channel complexes in the control of Mg2+ transport by epithelial cells.
Left: Apical localisation of TRPM6 protein in distal convoluted tubules of mouse kidney as assessed by a TRPM6-specific antibody.
Right: Current model of the role of TRPM6 and TRPM7 in transcellular Mg2+ transport. TRPM6 co-functions with TRPM7 to ensure a high rate of Mg2+ uptake by epithelial cells.