Molecular function and biological importance of CNNM family Mg 2+ transporters

Abstract

Cyclin M (CNNM) family proteins are evolutionarily conserved Mg 2+ transporters. They extrude Mg 2+ from cells and maintain intracellular Mg 2+ levels within the normal range. Moreover, they play an important role in Mg 2+ (re)absorption in the intestine and kidney by mediating the directional transport of Mg 2+ across epithelial tissue from the tubular lumen to the body inside. Mg 2+ efflux is suppressed by the direct binding with phosphatase of regenerating liver (PRL), and the formation of the complex is dynamically regulated by cysteine phosphorylation of PRL. The dysfunction of CNNM family proteins is responsible for inherited hypomagnesemia, as well as various intractable diseases, such as cancer and hypertension. Through multiple functional analyses of CNNM family proteins, the biomedical significance of the proper regulation of Mg 2+ levels has been elucidated.