Vandenberghe M, Raphaël M, Lehen'kyi V, Gordienko D, Hastie R, Oddos T, Rao A, Hogan PG, Skryma R, Prevarskaya N, et al.
Proceedings of the National Academy of Sciences of the United States of America. Date of publication 2013 Dec 10;volume 110(50):E4839-48.
1. Proc Natl Acad Sci U S A. 2013 Dec 10;110(50):E4839-48. doi:
10.1073/pnas.1310394110. Epub 2013 Nov 25.
ORAI1 calcium channel orchestrates skin homeostasis.
Vandenberghe M(1), Raphaël M, Lehen'kyi V, Gordienko D, Hastie R, Oddos T, Rao A,
Hogan PG, Skryma R, Prevarskaya N.
Author information:
(1)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.
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.
DOI: 10.1073/pnas.1310394110
PMCID: PMC3864283
PMID: 24277812 [Indexed for MEDLINE]
