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Epidermal TRPM8 channel isoform controls the balance between keratinocyte proliferation and differentiation in a cold-dependent manner.

par Bidaux, Gabriel;Borowiec, Anne-Sophie;Gordienko, Dmitri;Beck, Benjamin ;Shapovalov, George GG;Lemonnier, Loic;Flourakis, Matthieu;Vandenberghe, Matthieu;Slomianny, Christian;Dewailly, Etienne;Delcourt, Philippe;Desruelles, Emilie;Ritaine, Abigaël;Polakowska, Renata;Lesage, Jean;Chami, Mounia;Skryma, Roman;Prevarskaya, Natalia
Référence Proceedings of the National Academy of Sciences of the United States of America, 112, 26, page (E3345-E3354)
Publication Publié, 2015-06

Article révisé par les pairs

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Résumé :

Deviation of the ambient temperature is one of the most ubiquitous stimuli that continuously affect mammals' skin. Although the role of the warmth receptors in epidermal homeostasis (EH) was elucidated in recent years, the mystery of the keratinocyte mild-cold sensor remains unsolved. Here we report the cloning and characterization of a new functional epidermal isoform of the transient receptor potential M8 (TRPM8) mild-cold receptor, dubbed epidermal TRPM8 (eTRPM8), which is localized in the keratinocyte endoplasmic reticulum membrane and controls mitochondrial Ca(2+) concentration ([Ca(2+)]m). In turn, [Ca(2+)]m modulates ATP and superoxide ([Formula: see text]) synthesis in a cold-dependent manner. We report that this fine tuning of ATP and [Formula: see text] levels by cooling controls the balance between keratinocyte proliferation and differentiation. Finally, to ascertain eTRPM8's role in EH in vivo we developed a new functional knockout mouse strain by deleting the pore domain of TRPM8 and demonstrated that eTRPM8 knockout impairs adaptation of the epidermis to low temperatures.