Structure and function of the extracellular calcium-sensing receptor (Review)

The extracellular calcium-sensing receptor (CaR) originally cloned from bov ine parathyroid gland is a G protein-coupled receptor. The physiological re levance of the cloned CaR for sensing and regulating the extracellular calc ium concentration has been established by identifying hyper- and hypocalcem ic disorders resulting from inactivating and activating mutations, respecti vely, in the CaR. The cloned CaR has been stably or transiently expressed i n human embryonic kidney cells and significant progress has been made in el ucidating its biochemical and functional features using physiological, bioc hemical and molecular biological methods. A large collection of naturally o ccurring CaR mutations offers a valuable resource for studies aimed at unde rstanding the structure-function relationships of the receptor, including r eceptor-receptor interactions. In turn, characterization of these naturally occurring mutations has clarified the pathogenesis of clinical conditions involving abnormalities in the CaR, such as familial hypocalciuric hypercal cemia and neonatal severe hyperparathyroidism, and the physiology of certai n cell types, such as keratinocytes.