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J. Biol. Chem. 275 (2): 1183-1190

© 2000 by The American Society for Biochemistry and Molecular Biology, Inc.

The Calcium Sensing Receptor and Its Alternatively Spliced Form in Murine Epidermal Differentiation*

Yuko Oda{ddagger}§, Chia-Ling Tu, Wenhan Chang, Debra Crumrine{ddagger}, László Kömüves{ddagger}, Theodora Mauro{ddagger}, Peter M. Elias{ddagger}, , and Daniel D. Bikle

From the Departments of {ddagger}Medicine and Dermatology and Endocrinology, University of California San Francisco, Veterans Affairs Medical Center, San Francisco, California 94121

ABSTRACT Back to Top

Abstract: We have recently reported that human keratinocytes express both the full-length calcium sensing receptor (CaR) and an alternatively spliced form lacking exon 5, which were suggested to be involved in calcium induced keratinocyte differentiation. To understand further the role of these CaRs, we analyzed the structure of mouse CaRs, and investigated their role using a mouse model in which only the full-length CaR was disrupted. Our results show that both the full-length and the alternatively spliced variant lacking exon 5 encoding 77 amino acids of the extracellular domain were expressed in mouse epidermis. The deletion of the full-length CaR increased the production of the alternatively spliced form of CaR in mutant mice. The keratinocytes derived from these mutant mice did not respond to extracellular calcium, suggesting that the full-length CaR is required to mediate calcium signaling in the keratinocytes. The loss of the full-length CaR altered the morphologic appearance of the epidermis and resulted in a reduction of the mRNA and protein levels of the keratinocyte differentiation marker, loricrin. These results indicate that CaR is important in epidermal differentiation, and that the alternatively spliced form does not fully compensate for loss of the full-length CaR.


Received for publication August 19, 1999.

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