Loss-of-function and gain-of-function mutations of calcium-sensing receptor: Functional analysis and the effect of allosteric modulators NPS R-568 and NPS 2143

Journal of Clinical Endocrinology and Metabolism

Volumn 98, Issue 10, 2013, Pages

  Nakamura, Akie ^a   Hotsubo, Tomoyuki ^b   Kobayashi, Keiji ^c   Mochizuki, Hiroshi ^d   Ishizu, Katsura ^a   Tajima, Toshihiro ^a  

^a HOKKAIDO UNIVERSITY   (Japan)

^b Sapporo Medical Center   (Japan)

^c National Hospital Organization Nishisaitama Chuo National Hospital   (Japan)

^d SAITAMA CHILDREN'S MEDICAL CENTER   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ALFACALCIDOL; CALCIUM SENSING RECEPTOR; CREATININE; MITOGEN ACTIVATED PROTEIN KINASE; PARATHYROID HORMONE;

ABDOMINAL PAIN; ARTICLE; AUTOSOMAL DOMINANT HYPOPARATHYROIDISM; CALCIUM BLOOD LEVEL; CALCIUM EXCRETION; CASR GENE; CELL MEMBRANE; CLINICAL FEATURE; CONTROLLED STUDY; CREATININE URINE LEVEL; DNA SEQUENCE; FAMILIAL HYPOCALCIURIC HYPERCALCEMIA; FAMILY HISTORY; FEBRILE CONVULSION; GENE; GENE EXPRESSION; GENE MUTATION; HETEROZYGOSITY; HUMAN; HUMAN CELL; HYPERBILIRUBINEMIA; HYPERCALCEMIA; HYPOCALCIURIA; HYPOPARATHYROIDISM; IN VITRO STUDY; JAPANESE; PHOTOTHERAPY; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; SEQUENCE ANALYSIS; SIGNAL TRANSDUCTION; TACHYPNEA;

CHILD; HUMANS; HYPERCALCEMIA; HYPOPARATHYROIDISM; INFANT; INFANT, NEWBORN; MUTATION; RECEPTORS, CALCIUM-SENSING;

EID: 84885226730     PISSN: 0021972X     EISSN: 19457197     Source Type: Journal    
DOI: 10.1210/jc.2013-1974     Document Type: Article

References (32)

1. Brown EM, Gamba G, Riccaridi D, et al. Cloning and characterization of an extracellular Ca(2 +)-sensing receptor from bovine parathyroid. Nature. 1993; 366: 575-580.
2. Egbuna OI, Brown EM Hypercalcaemic and hypocalcaemic conditions due to calcium-sensing receptor mutations. Best Pract Res Clin Rheumatol. 2008; 22: 129-148.
3. Riccardi D, Brown EM Physiology and pathophysiology of the calcium-sensing receptor in the kidney. Am J Physiol Renal Physiol. 2010; 298: F485-F499.
4. Brown EM. The calcium-sensing receptor: physiology, pathophysiology and CaR-based therapeutics. Subcell Biochem. 2007; 45: 139-167.
5. Hu J, Spiegel AM Structure and function of the human calcium-sensing receptor: insights from natural and engineered mutations and allosteric modulators. J Cell Mol Med. 2007; 11: 908-922.
6. Pollak MR, Brown EM, Chou Y.H., et al Mutations in the human Ca(2 +)-sensing receptor gene cause familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism. Cell. 1993; 75: 1297-1303.
7. Pollak MR, Brown EM, Estep H.L., et al Autosomal dominant hypocalcaemia caused by a Ca(2 +)-sensing receptor gene mutation. Nat Genet. 1994; 8: 303-307.
8. Pearce SH, Williamson C, Kifor O., et al A familial syndrome of hypocalcemia with hypercalciuria due to mutations in the calcium-sensing receptor. N Engl J Med. 1996; 335: 1115-1122.
9. Nemeth EF, Steffey ME, Hammerland L.G., et al Calcimimetics with potent and selective activity on the parathyroid calcium receptor. Proc Natl Acad Sci USA. 1998; 95: 4040-4045.
10. Nemeth EF, Delmer EG, Heaton W.L., et al Calcilytic compounds: potent and selective Ca2+ receptor antagonists that stimulate secretion of parathyroid hormone. J Pharmacol Exp Ther.2001; 299: 323-331.
11. Ward DT, Riccardi D. New concepts in calcium-sensing receptor pharmacology and signaling. Br J Pharmacol. 2012; 165: 35-48.
12. Petrel C, Kessler A, Dauban P., Dodd RH, Rognan D, Ruat M. Positive and negative allosteric modulators of the Ca2+-sensing receptor interact within overlapping but not identical binding sites in the transmembrane domain. J Biol Chem. 2004; 279: 18990-18997.
13. Huang Y, Breitwieser GE Rescue of calcium-sensing receptor mutants by allosteric modulators reveals a conformational checkpoint in receptor biogenesis. J Biol Chem. 2007; 282: 9517-9525.
14. White E, McKenna J, Cavanaugh A., Breitwieser GE Pharmaco-chaperone- mediated rescue of calcium-sensing receptor loss-of function mutants. Mol Endocrinol. 2009; 23: 1115-1123.
15. Block GA, Martin KJ, de Francisco AL, et al Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis. N Engl J Med. 2004; 350: 1516-1525.
16. Timmers HJ, Karperien M, Hamdy N.A., de Boer H, Hermus AR Normalization of serum calcium by cinacalcet in a patient with hypercalcaemia due to a de novo inactivating mutation of the calcium-sensing receptor. J Intern Med. 2006; 260: 177-182.
17. Festen-Spanjer B., Haring CM, Koster J.B., Mudde AH Correction of hypercalcaemia by cinacalcet in familial hypocalciuric hypercalcaemia. Clin Endocrinol (Oxf). 2008; 68: 324-325.
18. Alon US, VandeVoorde RG Beneficial effect of cinacalcet in a child with familial hypocalciuric hypercalcemia. Pediatr Nephrol. 2010; 25: 1747-1750.
19. Hu J, McLarnon SJ, Mora S, et al A region in the seven-transmem-brane domain of the human Ca2 + receptor critical for response to Ca2 +. J Biol Chem. 2005; 280: 5113-5120.
20. Letz S, Rus R, Haag C., et al Novel activating mutations of the calcium-sensing receptor: the calcilytic NPS-2143 mitigates excessive signal transduction of mutant receptors. J Clin Endocrinol Metab. 2010; 95: E229-E233.
21. Park SY, Mun HC, Eom Y.S., et al 2012 Identification and characterization of D410E, a novel mutation in the loop 3 domain of CASR, in autosomal dominant hypocalcemia and a therapeutic approach using a novel calcilytic, AXT914. Clin Endocrinol (Oxf). 2013; 78(5): 687-689.
22. D'Souza-Li L, Yang B, Canaff L, et al. Identification and functional characterization of novel calcium-sensing receptor mutations in familial hypocalciuric hypercalcemia and autosomal dominant hypocalcemia. J Clin Endocrinol Metab. 2002; 87: 1309-1318.
23. Jap TS, Wu YC, Jenq S.F., Won GS A novel mutation in the calcium-sensing receptor gene in a Chinese subject with persistent hypercalcemia and hypocalciuria. J Clin Endocrinol Metab. 2001; 86: 13-15.
24. Lietman SA, Tenenbaum-Rakover Y, Jap T.S., et al A novel loss-of-function mutation, Gln459Arg, of the calcium-sensing receptor gene associated with apparent autosomal recessive inheritance of familial hypocalciuric hypercalcemia. J Clin Endocrinol Metab. 2009; 94: 4372-4379.
25. Watanabe S, Fukumoto S, Chang H., et al Association between activating mutations of calcium-sensing receptor and Bartter's syndrome. Lancet. 2002; 360: 692-694.
26. Terranegra A, Ferraretto A, Dogliotti E., et al Calcimimetic R-568 effects on activity of R990G polymorphism of calcium-sensing receptor. J Mol Endocrinol. 2010; 45: 245-256.
27. Nanjo K, Nagai S, Shimizu C., et al Identification and functional analysis of novel calcium-sensing receptor gene mutation in familial hypocalciuric hypercalcemia. Endocr J. 2010; 57: 787-792.
28. Cheng Z, Garvin D, Paguio A., Stecha P, Wood K, Fan F. Luciferase reporter assay system for deciphering GPCR pathways. Curr Chem Genomics. 2010; 4: 84-91.
29. Pidasheva S, Grant M, Canaff L., Ercan O, Kumar U, Hendy GN Calcium-sensing receptor dimerizes in the endoplasmic reticulum: biochemical and biophysical characterization of CASR mutants retained intracellularly. Hum Mol Genet. 2006; 15: 2200-2209.
30. Lienhardt A, Garabédian M, Bai M., et al A large homozygous or heterozygous in-frame deletion within the calcium-sensing receptor's carboxyl terminal cytoplasmic tail that causes autosomal dominant hypocalcemia. J Clin Endocrinol Metab. 2000; 85: 1695-1702.
31. Rus R, Haag C, Bumke-Vogt C, et al Novel inactivating mutations of the calcium-sensing receptor: the calcimimetic NPS R-568 improves signal transduction of mutant receptors. J Clin Endocrinol Metab. 2008; 93: 4797-4803.
32. Lee HJ, Mun HC, Lewis N.C., et al Allosteric activation of the extracellular Ca2 +-sensing receptor by L-amino acids enhances ERK1/2 phosphorylation. Biochem J. 2007; 404: 141-149.