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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).<ref name="pmid17117288">{{cite journal | author = D'Souza-Li L | title = The calcium-sensing receptor and related diseases | journal = Arquivos brasileiros de endocrinologia e metabologia | volume = 50 | issue = 4 | pages = 628–39 | year = 2006 | pmid = 17117288 | doi = 10.1590/S0004-27302006000400008 | issn = }}</ref>
The '''calcium-sensing receptor''' (CaSR) is a [[Class C GPCR|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).<ref name="pmid17117288">{{cite journal | author = D'Souza-Li L | title = The calcium-sensing receptor and related diseases | journal = Arquivos brasileiros de endocrinologia e metabologia | volume = 50 | issue = 4 | pages = 628–39 | year = 2006 | pmid = 17117288 | doi = 10.1590/S0004-27302006000400008 | issn = }}</ref>


==Signal transduction==
==Signal transduction==
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*{{cite journal | author=Ward BK, Stuckey BG, Gutteridge DH, ''et al.'' |title=A novel mutation (L174R) in the Ca2+-sensing receptor gene associated with familial hypocalciuric hypercalcemia. |journal=Hum. Mutat. |volume=10 |issue= 3 |pages= 233–5 |year= 1997 |pmid= 9298824 |doi= 10.1002/(SICI)1098-1004(1997)10:3<233::AID-HUMU9>3.0.CO;2-J }}
*{{cite journal | author=Ward BK, Stuckey BG, Gutteridge DH, ''et al.'' |title=A novel mutation (L174R) in the Ca2+-sensing receptor gene associated with familial hypocalciuric hypercalcemia. |journal=Hum. Mutat. |volume=10 |issue= 3 |pages= 233–5 |year= 1997 |pmid= 9298824 |doi= 10.1002/(SICI)1098-1004(1997)10:3<233::AID-HUMU9>3.0.CO;2-J }}
*{{cite journal | author=Quinn SJ, Kifor O, Trivedi S, ''et al.'' |title=Sodium and ionic strength sensing by the calcium receptor. |journal=J. Biol. Chem. |volume=273 |issue= 31 |pages= 19579–86 |year= 1998 |pmid= 9677383 |doi=10.1074/jbc.273.31.19579 }}
*{{cite journal | author=Quinn SJ, Kifor O, Trivedi S, ''et al.'' |title=Sodium and ionic strength sensing by the calcium receptor. |journal=J. Biol. Chem. |volume=273 |issue= 31 |pages= 19579–86 |year= 1998 |pmid= 9677383 |doi=10.1074/jbc.273.31.19579 }}
}}
*{{cite journal | author=Magno AL, Ward BK, Ratajczak T, |title=The calcium-sensing receptor: a molecular Perspective. |journal=Endocr Rev. |volume=32 |issue= 1 |pages= 3–30 |year= 2011 |pmid= 20729338 |doi=10.1210/er.2009-0043}}
*{{cite journal | author=Magno AL, Ward BK, Ratajczak T, |title=The calcium-sensing receptor: a molecular Perspective. |journal=Endocr Rev. |volume=32 |issue= 1 |pages= 3–30 |year= 2011 |pmid= 20729338 |doi=10.1210/er.2009-0043}}
}}
}}

Revision as of 04:27, 5 September 2011

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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

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

  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 (1999). "Calcium-sensing receptor and calcimimetic agents". Kidney Int. Suppl. 73: S52–8. PMID 10633465. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  4. ^ Costanzo, Linda S. (2007). BRS Physiology. Lippincott, Williams, & Wilkins. p. 260. ISBN 978-0781773119. {{cite book}}: Cite has empty unknown parameter: |coauthors= (help)
  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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  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.
  9. ^ Hjälm, G (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. 276 (37). United States: 34880–7. doi:10.1074/jbc.M100784200. ISSN 0021-9258. PMID 11390380. {{cite journal}}: Check date values in: |year= (help); Cite has empty unknown parameters: |laydate=, |laysummary=, and |laysource= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)CS1 maint: unflagged free DOI (link) CS1 maint: year (link)
  10. ^ Awata, H (2001). "Interaction of the calcium-sensing receptor and filamin, a potential scaffolding protein". J. Biol. Chem. 276 (37). United States: 34871–9. doi:10.1074/jbc.M100775200. ISSN 0021-9258. PMID 11390379. {{cite journal}}: Check date values in: |year= (help); Cite has empty unknown parameters: |laydate=, |laysummary=, and |laysource= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)CS1 maint: unflagged free DOI (link) CS1 maint: year (link)

Further reading

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