Homeothermic animals keep their body temperature in the optimum range. In many organisms, temperature-sensitive TRP (Transient Receptor Potential) channels (Large ion channel family activated by many kinds of stimuli, such as chemical, mechanical stimuli and temperature) engage in the function to sense temperature such as environmental temperature change. Interestingly, some of temperature-sensitive TRP channels are localized in deep organs maintained at core body temperature and activated by body temperature. So, we call them as “body temperature sensor”. TRPM2 (M; melastatin) is one of body temperature sensor. TRPM2 is broadly expressed in brain, liver, spleen, pancreas and immune cells.

  TRPM2 activity is regulated not only by temperature but also by intracellular Ca2+ ion, redox signal (intracellular oxidoreduction state working as signaling molecules) and intracellular TRPM2 activators, all reflect cellular metabolic state. We have intended to clarify the mechanism properly regulating TRPM2 activity at body temperature. As a result, we have revealed novel regulatory mechanism of TRPM2 function. TRPM2 activity at body temperature is increased by redox signal with the reduction of temperature threshold for TRPM2 activation. TRPM2 contributes temperature-dependent elevation of phagocytosis (the cellular function to engulf particle such as pathogen) and insulin secretion. In addition, TRPM2 has been reported to function in body temperature regulation. TRPM2 monitors temperature increase in hypothalamus, the body temperature control center, and in peripheral neurons. TRPM2 activation in these neurons seems to lead heat dissipation and cooler place-seeking behavior to decrease body temperature.

  These results suggest TRPM2 involvement in body temperature- and metabolism-based regulation of physiological functions in our body. Novel concept, TRPM2 as temperature-sensitive metabolic sensor, may pave the way to explore unknown TRPM2 functions.
 

 

Collaborative Researcher

Makiko KASHIO: Aichi Medical University