Fine-tuning of eTRPM8 expression and activity conditions keratinocyte fate

Recently, we reported the cloning and characterization of short isoform of the icilin-activated cold receptor TRPM8 channel in keratinocytes, dubbed eTRPM8. We demonstrated that eTRPM8 via fine tuning of the endoplasmic reticulum (ER) - mitochondria Ca 2+ shuttling regulates mitochondrial ATP and su...

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Bibliographic Details
Published in:Channels (Austin, Tex.) Tex.), 2016-07, Vol.10 (4), p.320-331
Main Authors: Bidaux, Gabriel, Borowiec, Anne-Sophie, Prevarskaya, Natalia, Gordienko, Dmitri
Format: Article
Language:English
Subjects:
Addendum
Adenosine Triphosphate - metabolism
Animals
ATP
bioenergetics
Calcium - metabolism
cell death
Cell Line
cell physiology
Cell Proliferation
Cytosol - metabolism
differentiation
Endoplasmic Reticulum - metabolism
epidermal homeostasis
Epidermis - cytology
Epidermis - metabolism
ER Calcium fluxes
eTRPM8
Gene Expression
Homeostasis
Humans
Keratinocytes - cytology
Keratinocytes - metabolism
Life Sciences
Mice
mild cold
mitochondria
Mitochondria - metabolism
proliferation
Protein Isoforms - genetics
Protein Isoforms - metabolism
ROS
Signal Transduction
superoxide
Superoxides - metabolism
TRPM Cation Channels - genetics
TRPM Cation Channels - metabolism
TRPM8 channels
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Summary:Recently, we reported the cloning and characterization of short isoform of the icilin-activated cold receptor TRPM8 channel in keratinocytes, dubbed eTRPM8. We demonstrated that eTRPM8 via fine tuning of the endoplasmic reticulum (ER) - mitochondria Ca 2+ shuttling regulates mitochondrial ATP and superoxide (O 2 *- ) production and, thereby, mediates control of epidermal homeostasis by mild cold. Here, we provide additional information explaining why eTRPM8 suppression and TRPM8 stimulation both inhibit keratinocyte growth. We also demonstrate that stimulation of eTRPM8 with icilin may give rise to sustained oscillatory responses. Furthermore, we show that ATP-induced cytosolic and mitochondrial Ca 2+ responses are attenuated by eTRPM8 suppression. This suggests positive interplay between eTRPM8 and purinergic signaling pathways, what may serve to facilitate the ER-mitochondria Ca 2+ shuttling. Finally, we demonstrate that cold (25°C) induces eTRPM8-dependent superoxide-mediated necrosis of keratinocytes. Altogether, these results are in line with our model of eTRPM8-mediated cold-dependent balance between keratinocyte proliferation and differentiation.
ISSN:1933-6950
1933-6969
DOI:10.1080/19336950.2016.1168551