Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Calcium Sensing Receptor (CASR)

  • Rakshya Gorkhali
  • Xiaojuan Tan
  • Jenny J. Yang
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101996

Synonyms

Historical Background

The calcium-sensing receptor (CaSR) is a heterotrimeric G-protein-coupled receptor (GPCR), one of the largest family of cell-surface receptors, containing 14 other members including the metabotropic glutamate receptors (mGluR) and ɣ-aminobutyric acid (GABA) B receptors (Zhang et al. 2016a). CaSR was first cloned by Dr. Edward M. Brown in 1993 from the bovine parathyroid gland (Brown et al. 1993). The major function of CaSR is to maintain calcium homeostasis by balancing the ingestion and absorption of calcium in the gastrointestinal tract, excretion of calcium through the urinary system, and the breakdown and formation of bone. CaSR regulates parathyroid hormone (PTH) secretion from parathyroid glands and calcitonin secretion from thyroidal C-cells upon sensing the alteration of the extracellular calcium concentration (Zhang et al. 2016a). This...

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Notes

Acknowledgments

This work was supported in part by National Institutes of Health Grants GM081749 and EB007268 and by the American Heart Association Grant 16GRNT31210016 (to J. J. Y.), and a Center for Diagnostics and Therapeutics fellowship (to R.G.) from Georgia State University.

References

  1. Breitwieser GE. Pharmacoperones and the calcium sensing receptor: exogenous and endogenous regulators. Pharmacol Res. 2014;83:30–7.PubMedCrossRefGoogle Scholar
  2. Brown EM, Gamba G, Riccardi D, Lombardi M, Butters R, Kifor O, et al. Cloning and characterization of an extracellular Ca(2+)-sensing receptor from bovine parathyroid. Nature. 1993;366(6455):575–80.PubMedCrossRefGoogle Scholar
  3. Colella M, Gerbino A, Hofer AM, Curci S. Recent advances in understanding the extracellular calcium-sensing receptor. F1000Res. 2016;5:1–12.CrossRefGoogle Scholar
  4. Conigrave AD, Ward DT. Calcium-sensing receptor (CaSR): pharmacological properties and signaling pathways. Best Pract Res Clin Endocrinol Metab. 2013;27(3):315–31.PubMedCrossRefGoogle Scholar
  5. Geng Y, Mosyak L, Kurinov I, Zuo H, Sturchler E, Cheng TC, et al. Structural mechanism of ligand activation in human calcium-sensing receptor. elife. 2016;5:1–25.Google Scholar
  6. Hannan FM, Nesbit MA, Zhang C, Cranston T, Curley AJ, Harding B, et al. Identification of 70 calcium-sensing receptor mutations in hyper- and hypo-calcaemic patients: evidence for clustering of extracellular domain mutations at calcium-binding sites. Hum Mol Genet. 2012;21(12):2768–78.PubMedCrossRefGoogle Scholar
  7. Hendy GN, Canaff L. Calcium-sensing receptor gene: regulation of Expression. Front Physiol. 2016;7:394.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Hendy GN, Guarnieri V, Canaff L. Calcium-sensing receptor and associated diseases. Prog Mol Biol Transl Sci. 2009;89:31–95.PubMedCrossRefGoogle Scholar
  9. Herberger AL, Loretz CA. Vertebrate extracellular calcium-sensing receptor evolution: selection in relation to life history and habitat. Comp Biochem Physiol Part D Genomics Proteomics. 2013;8(1):86–94.PubMedCrossRefGoogle Scholar
  10. Hizaki K, Yamamoto H, Taniguchi H, Adachi Y, Nakazawa M, Tanuma T, et al. Epigenetic inactivation of calcium-sensing receptor in colorectal carcinogenesis. Mod Pathol. 2011;24(6):876–84.PubMedCrossRefGoogle Scholar
  11. Huang Y, Zhou Y, Castiblanco A, Yang W, Brown EM, Yang JJ. Multiple Ca(2+)-binding sites in the extracellular domain of the Ca(2+)-sensing receptor corresponding to cooperative Ca(2+) response. Biochemistry. 2009;48(2):388–98.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Jeong S, Kim JH, Kim MG, Han N, Kim IW, Kim T, et al. Genetic polymorphisms of CASR and cancer risk: evidence from meta-analysis and HuGE review. Onco Targets Ther. 2016;9:655–69.PubMedPubMedCentralGoogle Scholar
  13. Leach K, Sexton PM, Christopoulos A, Conigrave AD. Engendering biased signalling from the calcium-sensing receptor for the pharmacotherapy of diverse disorders. Br J Pharmacol. 2014;171(5):1142–55.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Loretz CA. Extracellular calcium-sensing receptors in fishes. Comp Biochem Physiol A Mol Integr Physiol. 2008;149(3):225–45.PubMedCrossRefGoogle Scholar
  15. McGehee DS, Aldersberg M, Liu KP, Hsuing S, Heath MJ, Tamir H. Mechanism of extracellular Ca2+ receptor-stimulated hormone release from sheep thyroid parafollicular cells. J Physiol. 1997;502(Pt 1):31–44.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Saidak Z, Brazier M, Kamel S, Mentaverri R. Agonists and allosteric modulators of the calcium-sensing receptor and their therapeutic applications. Mol Pharmacol. 2009;76(6):1131–44.PubMedCrossRefGoogle Scholar
  17. Smajilovic S, Yano S, Jabbari R, Tfelt-Hansen J. The calcium-sensing receptor and calcimimetics in blood pressure modulation. Br J Pharmacol. 2011;164(3):884–93.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Ward BK, Magno AL, Walsh JP, Ratajczak T. The role of the calcium-sensing receptor in human disease. Clin Biochem. 2012;45(12):943–53.PubMedCrossRefGoogle Scholar
  19. Zhang C, Miller CL, Gorkhali R, Zou J, Huang K, Brown EM, et al. Molecular basis of the extracellular ligands mediated signaling by the calcium sensing receptor. Front Physiol. 2016a;7:441.PubMedPubMedCentralGoogle Scholar
  20. Zhang C, Zhang T, Zou J, Miller CL, Gorkhali R, Yang JY, et al. Structural basis for regulation of human calcium-sensing receptor by magnesium ions and an unexpected tryptophan derivative co-agonist. Sci Adv. 2016b;2(5):e1600241.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Rakshya Gorkhali
    • 1
  • Xiaojuan Tan
    • 1
  • Jenny J. Yang
    • 1
  1. 1.Georgia State UniversityAtlantaUSA