Calcium-sensing receptor
From Wikipedia, the free encyclopedia
| Calcium-sensing receptor | ||||||||
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| Identifiers | ||||||||
| Symbols | CASR; CAR; EIG8; FHH; FIH; GPRC2A; HHC; HHC1; NSHPT; PCAR1 | |||||||
| External IDs | OMIM: 601199 MGI: 1351351 HomoloGene: 332 IUPHAR: CaS ChEMBL: 1878 GeneCards: CASR Gene | |||||||
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| RNA expression pattern | ||||||||
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| Orthologs | ||||||||
| Species | Human | Mouse | ||||||
| Entrez | 846 | 12374 | ||||||
| Ensembl | ENSG00000036828 | ENSMUSG00000051980 | ||||||
| UniProt | P41180 | Q9QY96 | ||||||
| RefSeq (mRNA) | NM_000388.3 | NM_013803.2 | ||||||
| RefSeq (protein) | NP_000379.2 | NP_038831.2 | ||||||
| Location (UCSC) | Chr 3: 121.9 – 122.01 Mb |
Chr 16: 36.49 – 36.56 Mb |
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| PubMed search | [1] | [2] | ||||||
The calcium-sensing receptor (CaSR) is a Class C G-protein coupled receptor which senses extracellular levels of calcium ion. In the parathyroid gland, the calcium-sensing receptor controls calcium homeostasis by regulating the release of parathyroid hormone (PTH).[1]
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[edit] Signal transduction
The release of PTH is inhibited in response to elevations in plasma calcium concentrations and activation of the calcium receptor. Increased calcium binding on the extracellular side gives a conformational change in the receptor, which, on the intracellular side, initiates the phospholipase C pathway,[2][3] presumably through a Gqα type of G protein, which ultimately increases intracellular concentration of calcium, which inhibits vesicle fusion and exocytosis of parathyroid hormone. It also inhibits (not stimulates, as some[4] sources state) the cAMP dependent pathway.[3]
[edit] Pathology
Mutations that inactivate a CaSR gene cause Familial hypocalciuric hypercalcemia (FHH) (also known as Familial Benign Hypercalcemia because it is generally asymptomatic and does not require treatment),[5] when present in heterozygotes. Patients who are homozygous for CaSR inactivating mutations have more severe hypercalcemia.[6] Other mutations that activate CASR are the cause of autosomal dominant hypocalcemia[7] or Type 5 Bartter syndrome. An alternatively spliced transcript variant encoding 1088 aa has been found for this gene, but its full-length nature has not been defined.[8]
[edit] Therapeutic application
The drug cinacalcet is an allosteric modifier of the calcium-sensing receptor.[9] It is classified as a calcimimetic, which binds to the calcium-sensing receptor and decreases parathyroid hormone release.
[edit] Interactions
Calcium-sensing receptor has been shown to interact with Filamin.[10][11]
[edit] References
- ^ D'Souza-Li L (2006). "The calcium-sensing receptor and related diseases". Arquivos brasileiros de endocrinologia e metabologia 50 (4): 628–39. doi:10.1590/S0004-27302006000400008. PMID 17117288.
- ^ InterPro: IPR000068 GPCR, family 3, extracellular calcium-sensing receptor-related Retrieved on June 2, 2009
- ^ a b Coburn JW, Elangovan L, Goodman WG, Frazaõ JM (December 1999). "Calcium-sensing receptor and calcimimetic agents". Kidney Int. Suppl. 73: S52–8. PMID 10633465.
- ^ Costanzo, Linda S. (2007). pp. 260. ISBN 978-0-7817-7311-9. http://www.amazon.com/Physiology-Board-Review-Linda-Costanzo/dp/0781773113/.
- ^ Pidasheva S, Canaff L, Simonds WF, Marx SJ, Hendy GN (2005). "Impaired cotranslational processing of the calcium-sensing receptor due to signal peptide missense mutations in familial hypocalciuric hypercalcemia". Hum. Mol. Genet. 14 (12): 1679–90. doi:10.1093/hmg/ddi176. PMID 15879434.
- ^ Egbuna, O.; Brown, E. (2008). "Hypercalcaemic and hypocalcaemic conditions due to calcium-sensing receptor mutations". Best Practice & Research Clinical Rheumatology 22 (1): 129–148. doi:10.1016/j.berh.2007.11.006. PMC 2364635. PMID 18328986. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2364635/.
- ^ Mancilla EE, De Luca F, Baron J (1998). "Activating mutations of the Ca2+-sensing receptor". Mol. Genet. Metab. 64 (3): 198–204. doi:10.1006/mgme.1998.2716. PMID 9719629.
- ^ "Entrez Gene: CaSR calcium-sensing receptor (hypocalciuric hypercalcemia 1, severe neonatal hyperparathyroidism)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=846.
- ^ Torres PU (2006). "Cinacalcet HCl: a novel treatment for secondary hyperparathyroidism caused by chronic kidney disease". Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation 16 (3): 253–8. doi:10.1053/j.jrn.2006.04.010. PMID 16825031.
- ^ Hjälm, G; MacLeod R J, Kifor O, Chattopadhyay N, Brown E M (Sep. 2001). "Filamin-A binds to the carboxyl-terminal tail of the calcium-sensing receptor, an interaction that participates in CaR-mediated activation of mitogen-activated protein kinase". J. Biol. Chem. (United States) 276 (37): 34880–7. doi:10.1074/jbc.M100784200. ISSN 0021-9258. PMID 11390380.
- ^ Awata, H; Huang C, Handlogten M E, Miller R T (Sep. 2001). "Interaction of the calcium-sensing receptor and filamin, a potential scaffolding protein". J. Biol. Chem. (United States) 276 (37): 34871–9. doi:10.1074/jbc.M100775200. ISSN 0021-9258. PMID 11390379.
[edit] Further reading
- Hendy GN, D'Souza-Li L, Yang B et al. (2000). "Mutations of the calcium-sensing receptor (CASR) in familial hypocalciuric hypercalcemia, neonatal severe hyperparathyroidism, and autosomal dominant hypocalcemia". Hum. Mutat. 16 (4): 281–96. doi:10.1002/1098-1004(200010)16:4<281::AID-HUMU1>3.0.CO;2-A. PMID 11013439.
- Fukumoto S (2002). "[Calcium-sensing receptor in bone cells]". Nippon Rinsho 60 Suppl 3: 57–63. PMID 11979955.
- Tfelt-Hansen J, Schwarz P, Brown EM, Chattopadhyay N (2004). "The calcium-sensing receptor in human disease". Front. Biosci. 8: s377–90. doi:10.2741/1068. PMID 12700051.
- Hu J, Spiegel AM (2004). "Naturally occurring mutations of the extracellular Ca2+-sensing receptor: implications for its structure and function". Trends Endocrinol. Metab. 14 (6): 282–8. PMID 12890593.
- Aida K, Koishi S, Inoue M et al. (1995). "Familial hypocalciuric hypercalcemia associated with mutation in the human Ca(2+)-sensing receptor gene". J. Clin. Endocrinol. Metab. 80 (9): 2594–8. doi:10.1210/jc.80.9.2594. PMID 7673400.
- Aida K, Koishi S, Tawata M, Onaya T (1995). "Molecular cloning of a putative Ca(2+)-sensing receptor cDNA from human kidney". Biochem. Biophys. Res. Commun. 214 (2): 524–9. doi:10.1006/bbrc.1995.2318. PMID 7677761.
- Chou YH, Pollak MR, Brandi ML et al. (1995). "Mutations in the Human Ca2+-Sensing-Receptor Gene That Cause Familial Hypocalciuric Hypercalcemia". Am. J. Hum. Genet. 56 (5): 1075–9. PMC 1801464. PMID 7726161. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1801464/.
- Garrett JE, Capuano IV, Hammerland LG et al. (1995). "Molecular cloning and functional expression of human parathyroid calcium receptor cDNAs". J. Biol. Chem. 270 (21): 12919–25. doi:10.1074/jbc.270.21.12919. PMID 7759551.
- Pollak MR, Brown EM, Estep HL et al. (1995). "Autosomal dominant hypocalcaemia caused by a Ca(2+)-sensing receptor gene mutation". Nat. Genet. 8 (3): 303–7. doi:10.1038/ng1194-303. PMID 7874174.
- Pollak MR, Brown EM, Chou YH et al. (1994). "Mutations in the human Ca(2+)-sensing receptor gene cause familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism". Cell 75 (7): 1297–303. doi:10.1016/0092-8674(93)90617-Y. PMID 7916660.
- Janicic N, Soliman E, Pausova Z et al. (1996). "Mapping of the calcium-sensing receptor gene (CASR) to human chromosome 3q13.3-21 by fluorescence in situ hybridization, and localization to rat chromosome 11 and mouse chromosome 16". Mamm. Genome 6 (11): 798–801. doi:10.1007/BF00539007. PMID 8597637.
- Bikle DD, Ratnam A, Mauro T et al. (1996). "Changes in calcium responsiveness and handling during keratinocyte differentiation. Potential role of the calcium receptor". J. Clin. Invest. 97 (4): 1085–93. doi:10.1172/JCI118501. PMC 507156. PMID 8613532. //www.ncbi.nlm.nih.gov/pmc/articles/PMC507156/.
- Pearce SH, Trump D, Wooding C et al. (1996). "Calcium-sensing receptor mutations in familial benign hypercalcemia and neonatal hyperparathyroidism". J. Clin. Invest. 96 (6): 2683–92. doi:10.1172/JCI118335. PMC 185975. PMID 8675635. //www.ncbi.nlm.nih.gov/pmc/articles/PMC185975/.
- Bai M, Quinn S, Trivedi S et al. (1996). "Expression and characterization of inactivating and activating mutations in the human Ca2+o-sensing receptor". J. Biol. Chem. 271 (32): 19537–45. doi:10.1074/jbc.271.32.19537. PMID 8702647.
- Baron J, Winer KK, Yanovski JA et al. (1997). "Mutations in the Ca(2+)-sensing receptor gene cause autosomal dominant and sporadic hypoparathyroidism". Hum. Mol. Genet. 5 (5): 601–6. doi:10.1093/hmg/5.5.601. PMID 8733126.
- Freichel M, Zink-Lorenz A, Holloschi A et al. (1996). "Expression of a calcium-sensing receptor in a human medullary thyroid carcinoma cell line and its contribution to calcitonin secretion". Endocrinology 137 (9): 3842–8. doi:10.1210/en.137.9.3842. PMID 8756555.
- Chattopadhyay N, Ye C, Singh DP et al. (1997). "Expression of extracellular calcium-sensing receptor by human lens epithelial cells". Biochem. Biophys. Res. Commun. 233 (3): 801–5. doi:10.1006/bbrc.1997.6553. PMID 9168937.
- Cole DE, Janicic N, Salisbury SR, Hendy GN (1997). "Neonatal severe hyperparathyroidism, secondary hyperparathyroidism, and familial hypocalciuric hypercalcemia: multiple different phenotypes associated with an inactivating Alu insertion mutation of the calcium-sensing receptor gene". Am. J. Med. Genet. 71 (2): 202–10. doi:10.1002/(SICI)1096-8628(19970808)71:2<202::AID-AJMG16>3.0.CO;2-I. PMID 9217223.
- Ward BK, Stuckey BG, Gutteridge DH et al. (1997). "A novel mutation (L174R) in the Ca2+-sensing receptor gene associated with familial hypocalciuric hypercalcemia". Hum. Mutat. 10 (3): 233–5. doi:10.1002/(SICI)1098-1004(1997)10:3<233::AID-HUMU9>3.0.CO;2-J. PMID 9298824.
- Quinn SJ, Kifor O, Trivedi S et al. (1998). "Sodium and ionic strength sensing by the calcium receptor". J. Biol. Chem. 273 (31): 19579–86. doi:10.1074/jbc.273.31.19579. PMID 9677383.
- Magno AL, Ward BK, Ratajczak T, (2011). "The calcium-sensing receptor: a molecular Perspective". Endocr Rev. 32 (1): 3–30. doi:10.1210/er.2009-0043. PMID 20729338.
[edit] External links
- "Calcium-Sensing Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org/GPCR/ChapterMenuForward?chapterID=1322.
- CASRdb - Calcium Sensing Receptor Database, McGill University
- Receptors,+Calcium-Sensing at the US National Library of Medicine Medical Subject Headings (MeSH)
- CASR+protein at the US National Library of Medicine Medical Subject Headings (MeSH)
