Journal
NATURE REVIEWS ENDOCRINOLOGY
Volume 15, Issue 1, Pages 33-51Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41574-018-0115-0
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Funding
- Wellcome Trust Investigator Award [106995/Z/15/Z]
- National Institute for Health Research Senior Investigator Award [NF-SI-0514-10091]
- UK Medical Research Council [G9825289, G1000467]
- European Commission Seventh Framework Programme [FP7-264663]
- Horizon 2020 Programme of the European Union [675228]
- Austrian Science Fund [P29948-B28]
- Vienna Science and Technology Fund [LS12-047]
- US National Institute of Health Research Award [R01AR067291]
- Department of Veteran Affairs Merit Review Grant [I01 BX003453-01A2]
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [R01AR067291, P30AR066262] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK121656] Funding Source: NIH RePORTER
- Veterans Affairs [I01BX003453] Funding Source: NIH RePORTER
- MRC [G0601423, G1000467, G9825289] Funding Source: UKRI
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The Ca2+-sensing receptor (CaSR) is a dimeric family C G protein-coupled receptor that is expressed in calcitropic tissues such as the parathyroid glands and the kidneys and signals via G proteins and beta-arrestin. The CaSR has a pivotal role in bone and mineral metabolism, as it regulates parathyroid hormone secretion, urinary Ca2+ excretion, skeletal development and lactation. The importance of the CaSR for these calcitropic processes is highlighted by loss-of-function and gain-of-function CaSR mutations that cause familial hypocalciuric hypercalcaemia and autosomal dominant hypocalcaemia, respectively, and also by the fact that alterations in parathyroid CaSR expression contribute to the pathogenesis of primary and secondary hyperparathyroidism. Moreover, the CaSR is an established therapeutic target for hyperparathyroid disorders. The CaSR is also expressed in organs not involved in Ca2+ homeostasis: it has noncalcitropic roles in lung and neuronal development, vascular tone, gastrointestinal nutrient sensing, wound healing and secretion of insulin and enteroendocrine hormones. Furthermore, the abnormal expression or function of the CaSR is implicated in cardiovascular and neurological diseases, as well as in asthma, and the CaSR is reported to protect against colorectal cancer and neuroblastoma but increase the malignant potential of prostate and breast cancers.
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