TRPM2 causes sensitization to oxidative stress but attenuates high-temperature injury in the sea anemone Nematostella vectensis.

Wiebke Ehrlich, James M Gahan, Fabian Rentzsch, Frank J P Kühn

The Journal of experimental biology 2022 Mar 15

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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, with a C-terminally localized enzyme domain playing 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 investigated whether these evolutionary differences also apply to the physiological functions of TRPM2. For this purpose, we generated a TRPM2 loss-of-function mutation in N. vectensis 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 the two experimental groups to different stressors revealed that TRPM2 causes sensitization to oxidative stress but attenuates high-temperature injury in N. vectensis. 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 N. vectensis and open up the possibility of establishing N. vectensis as a model organism for the physiological function of TRPM2. © 2022. Published by The Company of Biologists Ltd.

Citation

Wiebke Ehrlich, James M Gahan, Fabian Rentzsch, Frank J P Kühn. TRPM2 causes sensitization to oxidative stress but attenuates high-temperature injury in the sea anemone Nematostella vectensis. The Journal of experimental biology. 2022 Mar 15;225(6)