The calcium sensing receptor and its alternatively spliced form in murine epidermal differentiation.
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.
Oda
Y
Y
Department of Medicine and Dermatology, University of California San Francisco, Veterans Affairs Medical Center, San Francisco, California 94121, USA. y2073@itsa.ucsf.edu
Tu
C L
CL
Chang
W
W
Crumrine
D
D
Kömüves
L
L
Mauro
T
T
Elias
P M
PM
Bikle
D D
DD
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D003001:Cloning, Molecular; D000078404:Epidermal Cells; D004817:Epidermis / Q000502:physiology; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012867:Skin / Q000166:cytology / Q000378:metabolism*; D014162:Transfection
D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D002118:Calcium