TRPM7

TRPM7 is a member of the transient receptor potential (TRP) channel family and is described as a channel-kinase, or “chanzyme.” It combines a six-transmembrane domain ion channel with a C-terminal alpha-kinase domain, enabling both ion conduction and protein phosphorylation. The channel portion forms a tetramer that conducts divalent cations, most notably magnesium (Mg2+) and calcium (Ca2+), while the kinase domain can phosphorylate substrate proteins.

Function and regulation are centered on cellular magnesium homeostasis. TRPM7 mediates Mg2+ influx, contributing to the intracellular Mg2+ pool required for numerous enzymatic processes. Channel activity is regulated by intracellular Mg2+ and Mg-ATP, providing a negative feedback mechanism: high Mg2+ or Mg-ATP inhibits channel opening, whereas low intracellular Mg2+ can relieve inhibition and promote flux. The kinase domain can autophosphorylate and may modulate channel activity and substrate phosphorylation, linking metal ion signaling to broader cellular pathways.

Expression and physiological roles are broad across tissues. TRPM7 is widely expressed in many cell types and is essential for normal development in mice; disruption causes embryonic lethality, indicating nonredundant roles in early development. Beyond development, TRPM7 participates in cell survival, proliferation, differentiation, and migration. In the nervous system, it supports neuronal growth and function; in other tissues, it contributes to magnesium homeostasis and cellular responses to stress.

Clinical significance is underscored by associations with disease processes and cellular pathology. Altered TRPM7 activity has been linked to cancer cell migration and invasion, ischemic injury, and various neurological conditions. Because of its dual channel-kinase nature and essential physiological roles, TRPM7 remains a focus of research for understanding magnesium signaling and as a potential therapeutic target, with approaches exploring channel blockers and modulators of kinase activity.