Matthieu Vandenberghe, Maylis Raphaël, V’yacheslav Lehen’kyi, Dmitri Gordienko, Ryan Hastie, Thierry Oddos, Anjana Rao, Patrick G. Hogan, Roman Skryma, and Natalia Prevarskaya
Institution
University Lille
Country
France
Year
2013
Journal
PNAS
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 Ca2+ channel that is a major molecular
counterpart for Ca2+ 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.