TRPM7: History of Two Functions

Among the more than 300 mammalian ion channels there are two unique members, TRPM6 and TRPM7, which are both ion channels and protein kinases (Chanzymes). TRPM6 and TRPM7 are ubiquitously expressed, with prominent roles in early embryonic development. Tissue-specific knockout mice indicate that TRPM7 is required for normal organ development of the heart and kidneys and complete KO is lethal beforeE8.

Similar to other TRPs, TRPM7 comprise tetrameric ion channel with each subunit containing six-transmembrane (6-TM) segments. However, unlike most TRP channels, TRPM7 is permeable to several divalent cations, including Zn2+, Mg2+, and Ca2+, as well as common monovalent cations such as Na+ and K+.

As chanzymes, the functions of TRPM6 and TRPM7 are correlated with proteolytic cleavage of the kinase domain, which is then translocated to the nucleus to phosphorylate histones and regulate gene expression.

Some of the unknown functions of these ion channels are: Is TRPM7 a channel or an enzyme? What activates the TRPM7 channel? What activates the protease that releases the TRPM7 kinase during development? Is TRPM7 primarily a plasma membrane or a vesicular protein?