The calcium-sensing receptor (CaSR) is a Class C

Class C GPCR

The class C G-protein-coupled receptors are a class of G-protein coupled receptors that include the metabotropic glutamate receptors and several additional receptors....

 G-protein coupled receptor which senses extracellular levels of calcium

Calcium

Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...

 ion. In the parathyroid gland

Parathyroid gland

The parathyroid glands are small endocrine glands in the neck that produce parathyroid hormone. Humans usually have four parathyroid glands, which are usually located on the rear surface of the thyroid gland, or, in rare cases, within the thyroid gland itself or in the chest...

, the calcium-sensing receptor controls calcium homeostasis

Homeostasis

Homeostasis is the property of a system that regulates its internal environment and tends to maintain a stable, constant condition of properties like temperature or pH...

 by regulating the release of parathyroid hormone

Parathyroid hormone

Parathyroid hormone , parathormone or parathyrin, is secreted by the chief cells of the parathyroid glands as a polypeptide containing 84 amino acids...

 (PTH).

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, presumably through a G_qα type of G protein

Gq alpha subunit

Gq protein or Gq/11 is a heterotrimeric G protein subunit that activates phospholipase C . PLC in turn hydrolyzes Phosphatidylinositol 4,5-bisphosphate to diacyl glycerol and inositol triphosphate signal transduction pathway...

, which ultimately increases intracellular concentration of calcium, which triggers vesicle fusion

Vesicle fusion

Vesicle fusion is the merging of a vesicle with other vesicles or a part of a cell membrane. In the latter case, it is the end stage of secretion from secretory vesicles, where their contents are expelled from the cell through exocytosis at the porosome...

 and exocytosis of parathyroid hormone. It also inhibits (not stimulates, as some sources state) the cAMP dependent pathway

CAMP dependent pathway

In the field of molecular biology, the cAMP-dependent pathway, also known as the adenylyl cyclase pathway, is a G protein-coupled receptor-triggered signaling cascade used in cell communication.-Mechanism:...

.

Pathology

Mutations that inactivate a CaSR gene cause Familial hypocalciuric hypercalcemia

Familial hypocalciuric hypercalcemia

-Causes:Types include:Most cases are associated with loss of function mutations in the CASR gene, which encodes a calcium-sensing receptor, expressed in parathyroid and kidney tissue...

(FHH) (also known as Familial Benign Hypercalcemia because it is generally asymptomatic and does not require treatment), when present in heterozygotes. Patients who are homozygous for CaSR inactivating mutations have more severe hypercalcemia. Other mutations that activate CASR are the cause of autosomal dominant hypocalcemia or Type 5 Bartter syndrome

Bartter syndrome

Bartter syndrome is a rare inherited defect in the thick ascending limb of the loop of Henle. It is characterized by low potassium levels , increased blood pH , and normal to low blood pressure. There are two types of Bartter syndrome: neonatal and classic...

. An alternatively spliced

Alternative splicing

Alternative splicing is a process by which the exons of the RNA produced by transcription of a gene are reconnected in multiple ways during RNA splicing...

 transcript variant encoding 1088 aa has been found for this gene, but its full-length nature has not been defined.

Therapeutic application

The drug cinacalcet

Cinacalcet

Cinacalcet is a drug that acts as a calcimimetic by allosteric activation of the calcium-sensing receptor that is expressed in various human organ tissues. It is sold by Amgen under the trade name Sensipar in North America and Australia and as Mimpara in Europe...

 is an allosteric modifier of the calcium-sensing receptor. 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

Protein-protein interaction

Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...

 with Filamin

Filamin

Filamins are a class of proteins that hold two actin filaments at large angles.Types include:* FLNA* FLNB* FLNC...

.

External links

• CASRdb - Calcium Sensing Receptor Database, McGill University
  McGill University
  Mohammed Fathy is a public research university located in Montreal, Quebec, Canada. The university bears the name of James McGill, a prominent Montreal merchant from Glasgow, Scotland, whose bequest formed the beginning of the university...