TRPM2 sensitizes to oxidative stress but attenuates high temperature injury in the sea anemone Nematostella vectensis

In humans, the cation channel TRPM2 (HsTRPM2) has been intensively studied because it is involved in oxidative stress mediated apoptosis and also contributes to temperature regulation. The gating mechanism of TRPM2 is quite complex where a C-terminally localized enzyme domain plays a crucial role. The analysis of orthologues of TRPM2, in particular from the distantly related marine invertebrate Nematostella vectensis (NvTRPM2) revealed that during evolution the functional role of the endogenous enzyme domain of TRPM2 has undergone fundamental changes. In this study we investigate whether these evolutionary differences also apply to the physiological functions of TRPM2. For this purpose, we generated a TRPM2 loss-of-function mutation in Nematostella and compared the phenotypes of wild-type and mutant animals after exposure to either oxidative stress or high temperature. Our results show that under standard culture conditions mutant animals are indistinguishable from wild-type animals in terms of morphology, and development. However, exposure of both experimental groups to different stressors revealed that TRPM2 sensitizes to oxidative stress but attenuates high temperature injury in Nematostella. Therefore, NvTRPM2 plays opposite roles in the cellular response to these two different stressors. These findings reveal a similar physiological spectrum of activity of TRPM2 in humans and Nematostella and open up the possibility to establish Nematostella as a model organism for the physiological function of TRPM2.