title: ORAI1 calcium channel orchestrates skin homeostasis.
abstract: To achieve and maintain skin architecture and homeostasis, keratinocytes must intricately balance growth, differentiation, and polarized motility known to be governed by calcium. Orai1 is a pore subunit of a store-operated Ca(2+) channel that is a major molecular counterpart for Ca(2+) influx in nonexcitable cells. To elucidate the physiological significance of Orai1 in skin, we studied its functions in epidermis of mice, with targeted disruption of the orai1 gene, human skin sections, and primary keratinocytes. We demonstrate that Orai1 protein is mainly confined to the basal layer of epidermis where it plays a critical role to control keratinocyte proliferation and polarized motility. Orai1 loss of function alters keratinocyte differentiation both in vitro and in vivo. Exploring underlying mechanisms, we show that the activation of Orai1-mediated calcium entry leads to enhancing focal adhesion turnover via a PKCβ-Calpain-focal adhesion kinase pathway. Our findings provide insight into the functions of the Orai1 channel in the maintenance of skin homeostasis.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1003, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Laboratory of Excellence Ion Channel Science and Therapeutics, Université des Sciences et Technologies de Lille, 59650 Villeneuve d'Ascq, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Vandenberghe
authors.forename: Maylis
authors.initials: M
authors.lastname: Raphaël
authors.forename: V'yacheslav
authors.initials: V
authors.lastname: Lehen'kyi
authors.forename: Dmitri
authors.initials: D
authors.lastname: Gordienko
authors.forename: Ryan
authors.initials: R
authors.lastname: Hastie
authors.forename: Thierry
authors.initials: T
authors.lastname: Oddos
authors.forename: Anjana
authors.initials: A
authors.lastname: Rao
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Hogan
authors.forename: Roman
authors.initials: R
authors.lastname: Skryma
authors.forename: Natalia
authors.initials: N
authors.lastname: Prevarskaya
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism / Q000502:physiology*; D022001:Focal Adhesions / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D000071740:ORAI1 Protein; D060888:Real-Time Polymerase Chain Reaction; D014945:Wound Healing / Q000502:physiology
chemical_list: D015220:Calcium Channels; D000071740:ORAI1 Protein; C520430:Orai1 protein, mouse
keywords: calcium signaling; cell migration; orai1 KO mice