Parathyroid hormone 1 receptor

Function

This "classical" PTH receptor is expressed in high levels in bone and kidney and regulates calcium ion homeostasis through activation of adenylate cyclase and phospholipase C. In bone, it is expressed on the surface of osteoblasts. When the receptor is activated through PTH binding, osteoblasts express RANKL (Receptor Activator of Nuclear Factor kB Ligand), which binds to RANK (Receptor Activator of Nuclear Factor kB) on osteoclasts. This turns on osteoclasts to ultimately increase the resorption rate.

Mechanism

It is a member of the secretin family of G protein-coupled receptors. The activity of this receptor is mediated by G_s G proteins which activate adenylyl cyclase. Besides, they also activate phosphatidylinositol-calcium second messenger system.

Pathology

Defects in this receptor are known to be the cause of Jansen's metaphyseal chondrodysplasia (JMC), chondrodysplasia Blomstrand type (BOCD), as well as enchondromatosis and primary failure of tooth eruption.

Interactions

Parathyroid hormone 1 receptor has been shown to interact with Sodium-hydrogen exchange regulatory cofactor 2 and Sodium-hydrogen antiporter 3 regulator 1.

Model organisms

Model organisms have been used in the study of PTH1R function. A conditional knockout mouse line called Pth1r^{tm1a(EUCOMM)Hmgu} was generated at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Additional screens performed: - In-depth immunological phenotyping