Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

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.

CaSR-mediated interactions between calcium and magnesium homeostasis in mice.
S. J. Quinn, A. R. B. Thomsen, O. Egbuna, J. Pang, K. Baxi, D. Goltzman, M. Pollak, and E. M. Brown (2013)
Am J Physiol Endocrinol Metab 304, E724-E733
   Abstract »    Full Text »    PDF »
Parathyroid Hormone-Independent Role for the Calcium-Sensing Receptor in the Control of Urinary Calcium Excretion.
D. Riccardi (2012)
J. Am. Soc. Nephrol. 23, 1766-1768
   Full Text »    PDF »
The calcium-sensing receptor complements parathyroid hormone-induced bone turnover in discrete skeletal compartments in mice.
Y. Xue, Y. Xiao, J. Liu, A. C. Karaplis, M. R. Pollak, E. M. Brown, D. Miao, and D. Goltzman (2012)
Am J Physiol Endocrinol Metab 302, E841-E851
   Abstract »    Full Text »    PDF »
A new role for the extracellular calcium-sensing receptor demonstrated by using CCK-eGFP BAC mice.
R. J. MacLeod (2011)
Am J Physiol Gastrointest Liver Physiol 300, G526-G527
   Full Text »    PDF »
The extracellular calcium-sensing receptor is required for cholecystokinin secretion in response to L-phenylalanine in acutely isolated intestinal I cells.
A. P. Liou, Y. Sei, X. Zhao, J. Feng, X. Lu, C. Thomas, S. Pechhold, H. E. Raybould, and S. A. Wank (2011)
Am J Physiol Gastrointest Liver Physiol 300, G538-G546
   Abstract »    Full Text »    PDF »
Atomic layer deposition-based functionalization of materials for medical and environmental health applications.
R. J. Narayan, S. P. Adiga, M. J. Pellin, L. A. Curtiss, A. J. Hryn, S. Stafslien, B. Chisholm, C.-C. Shih, C.-M. Shih, S.-J. Lin, et al. (2010)
Phil Trans R Soc A 368, 2033-2064
   Abstract »    Full Text »    PDF »
The calcium-sensing receptor (CaSR) defends against hypercalcemia independently of its regulation of parathyroid hormone secretion.
L. Kantham, S. J. Quinn, O. I. Egbuna, K. Baxi, R. Butters, J. L. Pang, M. R. Pollak, D. Goltzman, and E. M. Brown (2009)
Am J Physiol Endocrinol Metab 297, E915-E923
   Abstract »    Full Text »    PDF »
The full-length calcium-sensing receptor dampens the calcemic response to 1{alpha},25(OH)2 vitamin D3 in vivo independently of parathyroid hormone.
O. Egbuna, S. Quinn, L. Kantham, R. Butters, J. Pang, M. Pollak, D. Goltzman, and E. Brown (2009)
Am J Physiol Renal Physiol 297, F720-F728
   Abstract »    Full Text »    PDF »
Calcium-Sensing Receptor Activation Depresses Synaptic Transmission.
C. G. Phillips, M. T. Harnett, W. Chen, and S. M. Smith (2008)
J. Neurosci. 28, 12062-12070
   Abstract »    Full Text »    PDF »
The Extracellular Calcium-Sensing Receptor (CaSR) Is a Critical Modulator of Skeletal Development.
W. Chang, C. Tu, T.-H. Chen, D. Bikle, and D. Shoback (2008)
Science Signaling 1, ra1
   Abstract »    Full Text »    PDF »
New Insights in Bone Biology: Unmasking Skeletal Effects of the Extracellular Calcium-Sensing Receptor.
E. M. Brown and J. B. Lian (2008)
Science Signaling 1, pe40
   Abstract »    Full Text »    PDF »
Inactivation of the Calcium Sensing Receptor Inhibits E-cadherin-mediated Cell-Cell Adhesion and Calcium-induced Differentiation in Human Epidermal Keratinocytes.
C.-L. Tu, W. Chang, Z. Xie, and D. D. Bikle (2008)
J. Biol. Chem. 283, 3519-3528
   Abstract »    Full Text »    PDF »
TRPV6 Is a Ca2+ Entry Channel Essential for Ca2+-induced Differentiation of Human Keratinocytes.
V. Lehen'kyi, B. Beck, R. Polakowska, M. Charveron, P. Bordat, R. Skryma, and N. Prevarskaya (2007)
J. Biol. Chem. 282, 22582-22591
   Abstract »    Full Text »    PDF »
Simulating psoriasis by altering transit amplifying cells.
N. Grabe and K. Neuber (2007)
Bioinformatics 23, 1309-1312
   Abstract »    Full Text »    PDF »
Vitamin D and Skin Cancer.
D. D. Bikle (2004)
J. Nutr. 134, 3472S-3478S
   Abstract »    Full Text »    PDF »
Ca2+-stimulated Ca2+ Oscillations Produced by the Ca2+-sensing Receptor Require Negative Feedback by Protein Kinase C.
S. H. Young, S. V. Wu, and E. Rozengurt (2002)
J. Biol. Chem. 277, 46871-46876
   Abstract »    Full Text »    PDF »
Extracellular calcium sensing receptor in human pancreatic cells.
G Z Racz, A Kittel, D Riccardi, R M Case, A C Elliott, and G Varga (2002)
Gut 51, 705-711
   Abstract »    Full Text »    PDF »
A zinc-sensing receptor triggers the release of intracellular Ca2+ and regulates ion transport.
M. Hershfinkel, A. Moran, N. Grossman, and I. Sekler (2001)
PNAS 98, 11749-11754
   Abstract »    Full Text »    PDF »
Ras-independent Activation of the Raf/MEK/ERK Pathway upon Calcium-induced Differentiation of Keratinocytes.
M. Schmidt, M. Goebeler, G. Posern, S. M. Feller, C. S. Seitz, E.-B. Brocker, U. R. Rapp, and S. Ludwig (2000)
J. Biol. Chem. 275, 41011-41017
   Abstract »    Full Text »    PDF »
Ras-independent activation of the Raf/MEK/Erk pathway upon calcium-induced differentiation of keratinocytes.
M. Schmidt, M. Goebeler, G. Posern, S. M. Feller, C. S. Seitz, E.-B. Brocker, U. R. Rapp, and S. Ludwig (2000)
J. Biol. Chem.
   Abstract »
The Extracellular Calcium-sensing Receptor Is Required for Calcium-induced Differentiation in Human Keratinocytes.
C.-L. Tu, W. Chang, and D. D. Bikle (2001)
J. Biol. Chem. 276, 41079-41085
   Abstract »    Full Text »    PDF »
Amino acids and Ca2+ stimulate different patterns of Ca2+ oscillations through the Ca2+-sensing receptor.
S. H. Young and E. Rozengurt (2002)
Am J Physiol Cell Physiol 282, C1414-C1422
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882