The distinct roles of the N-terminal and C-terminal ADP-ribose binding sites in TRPM2 channel

TRPM2 is a calcium-permeable, non-selective cation channel present in different species from unicellular Choanoflagellates to human. TRPM2 plays an important role in the survival of early species and is critically involved in diverse physiological processes including core body temperature regulation, immune response, insulin secretion, and apoptosis. TRPM2 is polymodal and can be activated by a wide range of stimuli including warm temperature, oxidative stress and NAD+-related metabolites such as ADP-ribose (ADPR).