Calcium-sensing receptor

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Calcium-sensing receptor (hypocalciuric hypercalcemia 1, severe neonatal hyperparathyroidism)
Identifiers
SymbolsCASR; CAR; FHH; FIH; GPRC2A; HHC; HHC1; MGC138441; NSHPT; PCAR1
External IDsOMIM601199 MGI1351351 HomoloGene332 IUPHAR: CaS GeneCards: CASR Gene
RNA expression pattern
250px
250px
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez84612374
EnsemblENSG00000036828ENSMUSG00000051980
UniProtP41180O88982
RefSeq (mRNA)NM_000388NM_013803
RefSeq (protein)NP_000379NP_038831
Location (UCSC)Chr 3:
123.39 - 123.49 Mb
Chr 16:
36.41 - 36.48 Mb
PubMed search[1][2]

The calcium-sensing receptor (CaSR) is a 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]

Signal transduction

The release of PTH is inhibited in response to elevations in plasma calcium concentrations and activation of the calcium receptor. Decreased calcium binding on the extracellular side gives a conformation change in the receptor, which, on the intracellular side, initiates the phospholipase C pathway,[2][3] presumably through a G type of G protein, which ultimately increases intracellular concentration of calcium, which triggers vesicle fusion and exocytosis of parathyroid hormone. It also inhibits (not stimulates, as some[4] sources state) the cAMP dependent pathway.[3]

Pathology

Mutations that inactivate CASR cause familial hypocalciuric hypercalcemia (FHH) (also known as Familial Benign Hypercalcemia because it is generally asymptomatic and does not require treatment),[5] whereas mutations that activate CASR are the cause of autosomal dominant hypocalcemia[6] 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.[7]

Therapeutic application

The drug cinacalcet is an allosteric modifier of the calcium-sensing receptor.[8] It is classified as a calcimimetic, which binds to the calcium-sensing receptor and decreases parathyroid hormone release.

Interactions

Calcium-sensing receptor has been shown to interact with Filamin.[9][10]

References

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Further reading

External links

de:Calciumsensitiver Rezeptor

es:Receptor sensor de calcio he:קולטן לסידן

ja:カルシウム感知受容体
  1. 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. 
  2. InterPro: IPR000068 GPCR, family 3, extracellular calcium-sensing receptor-related Retrieved on June 2, 2009
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  4. Costanzo, Linda S. (2007). BRS Physiology. Lippincott, Williams, & Wilkins. p. 260. ISBN 978-0781773119. 
  5. 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. 
  6. 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. 
  7. "Entrez Gene: CASR calcium-sensing receptor (hypocalciuric hypercalcemia 1, severe neonatal hyperparathyroidism)". 
  8. 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. 
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