Extracellular calcium-sensing receptor

Definition:

G-protein-coupled receptor that senses changes in the extracellular concentration of calcium ions and plays a key role in maintaining calcium homeostasis. Senses fluctuations in the circulating calcium concentration and modulates the production of parathyroid hormone (PTH) in parathyroid glands (By similarity). The activity of this receptor is mediated by a G-protein that activates a phosphatidylinositol-calcium second messenger system. The G-protein-coupled receptor activity is activated by a co-agonist mechanism: aromatic amino acids, such as Trp or Phe, act concertedly with divalent cations, such as calcium or magnesium, to achieve full receptor activation.

References:

[1]. Piero Stratta, et al. Calcium-sensing-related gene mutations in hypercalcaemic hypocalciuric patients as differential diagnosis from primary hyperparathyroidism: detection of two novel inactivating mutations in an Italian population. Nephrol Dial Transplant. 2014 Oct;29(10):1902-9. [Content Brief]

[2]. Yong Geng, et al. Structural mechanism of ligand activation in human calcium-sensing receptor. Elife. 2016 Jul 19;5:e13662. [Content Brief]

[3]. Vito Guarnieri, et al. CASR gene activating mutations in two families with autosomal dominant hypocalcemia. Mol Genet Metab. 2012 Nov;107(3):548-52. [Content Brief]

[4]. J E Garrett, et al. Molecular cloning and functional expression of human parathyroid calcium receptor cDNAs. J Biol Chem. 1995 May 26;270(21):12919-25. [Content Brief]

[5]. Eugenio Mastromatteo, et al. A novel mutation in calcium-sensing receptor gene associated to hypercalcemia and hypercalciuria. BMC Endocr Disord. 2014 Oct 7;14:81. [Content Brief]

[6]. M Bai, et al. Expression and characterization of inactivating and activating mutations in the human Ca2+o-sensing receptor. J Biol Chem. 1996 Aug 9;271(32):19537-45. [Content Brief]

[7]. S H Pearce, et al. Functional characterization of calcium-sensing receptor mutations expressed in human embryonic kidney cells. J Clin Invest. 1996 Oct 15;98(8):1860-6. [Content Brief]

[8]. Natalia Baran, et al. Novel activating mutation of human calcium-sensing receptor in a family with autosomal dominant hypocalcaemia. Mol Cell Endocrinol. 2015 May 15;407:18-25. [Content Brief]

[9]. Abdallah Al-Salameh, et al. A novel mutation in the calcium-sensing receptor in a French family with familial hypocalciuric hypercalcaemia. Eur J Endocrinol. 2011 Aug;165(2):359-63. [Content Brief]

[10]. Eun Sook Kim, et al. Identification and functional analysis of a novel CaSR mutation in a family with familial hypocalciuric hypercalcemia. J Bone Miner Metab. 2016 Nov;34(6):662-667. [Content Brief]

[11]. Michael P Grant, et al. Agonist-driven maturation and plasma membrane insertion of calcium-sensing receptors dynamically control signal amplitude. Sci Signal. 2011 Nov 22;4(200):ra78. [Content Brief]

[12]. Chen Zhang, et al. Structural basis for regulation of human calcium-sensing receptor by magnesium ions and an unexpected tryptophan derivative co-agonist. Sci Adv. 2016 May 27;2(5):e1600241. [Content Brief]

[13]. Akie Nakamura, et al. 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. J Clin Endocrinol Metab. 2013 Oct;98(10):E1692-701. [Content Brief]

[14]. H Heath 3rd, et al. Clustered inactivating mutations and benign polymorphisms of the calcium receptor gene in familial benign hypocalciuric hypercalcemia suggest receptor functional domains. J Clin Endocrinol Metab. 1996 Apr;81(4):1312-7. [Content Brief]

[15]. Judit Tõke, et al. Neonatal severe hyperparathyroidism associated with a novel de novo heterozygous R551K inactivating mutation and a heterozygous A986S polymorphism of the calcium-sensing receptor gene. Clin Endocrinol (Oxf). 2007 Sep;67(3):385-92. [Content Brief]

[16]. Steven A Lietman, 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 Nov;94(11):4372-9. [Content Brief]

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