Abstract
The molecular characterization of the genes encoding the transient receptor potential (TRP) cation channels found in Drosophila photoreceptors gave rise to a systematic cloning strategy for mammalian isoforms. Using expressed sequence tag (EST) and genomic database searches, at least 20 new mammalian TRP-related genes have been cloned and the resulting channels characterized. The focus of this presentation will be on TRPM7 (LTRPC7, ChaK1, TRP-PLIK), a member of the TRPM channel subfamily. TRPM7 is a ubiquitously expressed and constitutively active divalent cation-selective ion channel, whose basal activity is regulated by intracellular levels of Mg2+ and Mg·ATP. Most interestingly, TRPM7 is a dual-function plasma membrane protein that acts both as an ion channel and as a protein kinase, whereby the protein's C-terminal alpha kinase domain proves not to be essential for the gating of the channel. Electrophysiological characterization of TRPM7 shows that the ion channel functions as a Ca2+- and Mg2+-permeable cation channel. Thus, endogenous TRPM7-like currents have been named MagNuM, for Magnesium-Nucleotide-regulated Metal ion currents. TRPM7 plays an essential role in cell proliferation and viability, which is implicated by the fact that cells made deficient in TRPM7 experience grow arrest within 24 hours and eventually die. Furthermore, most recent data provide evidence that TRPM7 regulates Mg2+ homeostasis in vertebrates. [Jpn J Physiol 54 Suppl:S36 (2004)]
