Calcium-sensing receptor

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Calcium-sensing receptor
Identifiers
Symbols CASR ; CAR; EIG8; FHH; FIH; GPRC2A; HHC; HHC1; NSHPT; PCAR1
External IDs OMIM601199 MGI1351351 HomoloGene332 IUPHAR: CaS ChEMBL: 1878 GeneCards: CASR Gene
RNA expression pattern
PBB GE CASR 210577 at tn.png
PBB GE CASR 211384 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 846 12374
Ensembl ENSG00000036828 ENSMUSG00000051980
UniProt P41180 Q9QY96
RefSeq (mRNA) NM_000388 NM_013803
RefSeq (protein) NP_000379 NP_038831
Location (UCSC) Chr 3:
121.9 – 122.01 Mb
Chr 16:
36.49 – 36.56 Mb
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]

Signal transduction[edit]

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 G 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]

Pathology[edit]

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]

Therapeutic application[edit]

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.

Interactions[edit]

Calcium-sensing receptor has been shown to interact with Filamin.[10][11]

References[edit]

  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
  3. ^ 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. 
  4. ^ Costanzo, Linda S. (2007). BRS Physiology (Board Review Series). p. 260. ISBN 978-0-7817-7311-9. 
  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. ^ 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.  edit
  7. ^ 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. 
  8. ^ "Entrez Gene: CaSR calcium-sensing receptor (hypocalciuric hypercalcemia 1, severe neonatal hyperparathyroidism)". 
  9. ^ 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. 
  10. ^ 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. 
  11. ^ 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. 

Further reading[edit]

External links[edit]