Referenced in: none

Automatically associated channels: TRP , TRPM , TRPM8

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

Authors: Gabriel Bidaux, Anne-Sophie Borowiec, Dmitri Gordienko, Benjamin Beck, George G Shapovalov, Loic Lemonnier, Matthieu Flourakis, Matthieu Vandenberghe, Christian Slomianny, Etienne Dewailly, Philippe Delcourt, Emilie Desruelles, Abigael Ritaine, Renata Polakowska, Jean Lesage, Mounia Chami, Roman Skryma, Natalia Prevarskaya

Journal, date & volume: Proc. Natl. Acad. Sci. U.S.A., 2015 Jun 30 , 112, E3345-54

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/26080404

Abstract
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 (O2(·-)) synthesis in a cold-dependent manner. We report that this fine tuning of ATP and O2(·-) 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.