Calcium regulation of keratinocyte differentiation

Abstract

Calcium is the major regulator of keratinocyte differentiation in vivo and in vitro. A calcium gradient within the epidermis promotes the sequential differentiation of keratinocytes as they traverse the different layers of the epidermis to form the permeability barrier of the stratum corneum. Calcium promotes differentiation by both outside–in and inside–out signaling. A number of signaling pathways involved with differentiation are regulated by calcium, including the formation of desmosomes, adherens junctions and tight junctions, which maintain cell–cell adhesion and play an important intracellular signaling role through their activation of various kinases and phospholipases that produce second messengers that regulate intracellular free calcium and PKC activity, critical for the differentiation process. The calcium receptor plays a central role by initiating the intracellular signaling events that drive differentiation in response to extracellular calcium. This review will discuss these mechanisms.

Keywords::

• cadherin
• calcium
• calcium receptor
• catenin
• keratinocyte
• phospholipase
• protein kinase C
• Src kinase

Acknowledgements

The authors acknowledge the administrative support of Teresa Tong and the efforts of a number of previous postdoctoral fellows in the laboratory who contributed to this work, including Kumar Pillai, Maria-Laura Mancianti, Mei-Ji Su, Anita Ratnam, David Gibson, Dean Ng, J-K Cho and L-C Yang, and key collaborators including Peter Elias, Kenneth Feingold, Theodora Mauro, Wenhan Chang, Lazlo Komuves and Yuko Oda.

Financial & competing interests disclosure

DD Bikle is supported by grants VA Merit Review, NIH RO1 AR050023 and DOD CA110338. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.