Calcitonin receptor explained

The calcitonin receptor (CT) is a G protein-coupled receptor that binds the peptide hormone calcitonin and is involved in maintenance of calcium homeostasis,^[1] particularly with respect to bone formation and metabolism.^{[2] [3] [4]}

CT works by activating the G-proteins G_s and G_q often found on osteoclasts, on cells in the kidney, and on cells in a number of regions of the brain.^[5] It may also affect the ovaries in women and the testes in men.

The function of the CT receptor protein is modified through its interaction with Receptor activity-modifying proteins (RAMPs), forming the multimeric amylin receptors AMY₁ (CT + RAMP1), AMY₂ (CT + RAMP2), and AMY₃ (CT+ RAMP3).^[6]

Preclinical studies have suggested that dual amylin and calcitonin receptor agonists may be more effective than amylin receptor agonists for obesity and type II diabetes.^[7]

Interactions

Calcitonin receptor has been shown to interact with Apolipoprotein B^{[8] [9]} and LRP1.^[10]

References

1. Purdue BW, Tilakaratne N, Sexton PM . Molecular pharmacology of the calcitonin receptor . Receptors & Channels . 8 . 3–4 . 243–55 . 2002 . 12529940 . 10.1080/10606820213681 .
2. Chambers TJ, Magnus CJ . Calcitonin alters behaviour of isolated osteoclasts . The Journal of Pathology . 136 . 1 . 27–39 . January 1982 . 7057295 . 10.1002/path.1711360104 . 8395420 .
3. Dacquin R, Davey RA, Laplace C, Levasseur R, Morris HA, Goldring SR, Gebre-Medhin S, Galson DL, Zajac JD, Karsenty G . Amylin inhibits bone resorption while the calcitonin receptor controls bone formation in vivo . The Journal of Cell Biology . 164 . 4 . 509–14 . February 2004 . 14970190 . 2171986 . 10.1083/jcb.200312135 .
4. Davey RA, Turner AG, McManus JF, Chiu WS, Tjahyono F, Moore AJ, Atkins GJ, Anderson PH, Ma C, Glatt V, MacLean HE, Vincent C, Bouxsein M, Morris HA, Findlay DM, Zajac JD . Calcitonin receptor plays a physiological role to protect against hypercalcemia in mice . Journal of Bone and Mineral Research . 23 . 8 . 1182–93 . August 2008 . 18627265 . 2680171 . 10.1359/jbmr.080310 .
5. http://senselab.med.yale.edu/NeuronDB/receptors2.asp#Neuropeptide%20Y%20receptors, senselab
6. Web site: Calcitonin Receptors: Introduction . IUPHAR Database of Receptors and Ion Channels . International Union of Basic and Clinical Pharmacology . 2008-12-12 . 2016-03-03 . https://web.archive.org/web/20160303193818/http://www.iuphar-db.org/GPCR/IntroductionDisplayForward?chapterID=1358 . dead .
7. Sonne . Nina . Karsdal . Morten A. . Henriksen . Kim . Mono and dual agonists of the amylin, calcitonin, and CGRP receptors and their potential in metabolic diseases . Molecular Metabolism . 1 April 2021 . 46 . 101109 . 10.1016/j.molmet.2020.101109 . 33166741 . 8085567 . 2212-8778. free .
8. Zhang J, Herscovitz H . Nascent lipidated apolipoprotein B is transported to the Golgi as an incompletely folded intermediate as probed by its association with network of endoplasmic reticulum molecular chaperones, GRP94, ERp72, BiP, calreticulin, and cyclophilin B . The Journal of Biological Chemistry . 278 . 9 . 7459–68 . February 2003 . 12397072 . 10.1074/jbc.M207976200 . free .
9. Linnik KM, Herscovitz H . Multiple molecular chaperones interact with apolipoprotein B during its maturation. The network of endoplasmic reticulum-resident chaperones (ERp72, GRP94, calreticulin, and BiP) interacts with apolipoprotein b regardless of its lipidation state . The Journal of Biological Chemistry . 273 . 33 . 21368–73 . August 1998 . 9694898 . 10.1074/jbc.273.33.21368 . free .
10. Orr AW, Pedraza CE, Pallero MA, Elzie CA, Goicoechea S, Strickland DK, Murphy-Ullrich JE . Low density lipoprotein receptor-related protein is a calreticulin coreceptor that signals focal adhesion disassembly . The Journal of Cell Biology . 161 . 6 . 1179–89 . June 2003 . 12821648 . 2172996 . 10.1083/jcb.200302069 .

Further reading

• Pondel M . Calcitonin and calcitonin receptors: bone and beyond . International Journal of Experimental Pathology . 81 . 6 . 405–22 . December 2000 . 11298188 . 2517743 . 10.1046/j.1365-2613.2000.00176.x .
• Gorn AH, Lin HY, Yamin M, Auron PE, Flannery MR, Tapp DR, Manning CA, Lodish HF, Krane SM, Goldring SR . Cloning, characterization, and expression of a human calcitonin receptor from an ovarian carcinoma cell line . The Journal of Clinical Investigation . 90 . 5 . 1726–35 . November 1992 . 1331173 . 443230 . 10.1172/JCI116046 .
• Albrandt K, Brady EM, Moore CX, Mull E, Sierzega ME, Beaumont K . Molecular cloning and functional expression of a third isoform of the human calcitonin receptor and partial characterization of the calcitonin receptor gene . Endocrinology . 136 . 12 . 5377–84 . December 1995 . 7588285 . 10.1210/endo.136.12.7588285 .
• Egerton M, Needham M, Evans S, Millest A, Cerillo G, McPheat J, Popplewell M, Johnstone D, Hollis M . Identification of multiple human calcitonin receptor isoforms: heterologous expression and pharmacological characterization . Journal of Molecular Endocrinology . 14 . 2 . 179–89 . April 1995 . 7619207 . 10.1677/jme.0.0140179 .
• Nussenzveig DR, Mathew S, Gershengorn MC . Alternative splicing of a 48-nucleotide exon generates two isoforms of the human calcitonin receptor . Endocrinology . 136 . 5 . 2047–51 . May 1995 . 7720653 . 10.1210/endo.136.5.7720653 .
• Nakamura M, Hashimoto T, Nakajima T, Ichii S, Furuyama J, Ishihara Y, Kakudo K . A new type of human calcitonin receptor isoform generated by alternative splicing . Biochemical and Biophysical Research Communications . 209 . 2 . 744–51 . April 1995 . 7733946 . 10.1006/bbrc.1995.1562 .
• Pérez Jurado LA, Li X, Francke U . The human calcitonin receptor gene (CALCR) at 7q21.3 is outside the deletion associated with the Williams syndrome . Cytogenetics and Cell Genetics . 70 . 3–4 . 246–9 . 1995 . 7789182 . 10.1159/000134044 .
• Nussenzveig DR, Thaw CN, Gershengorn MC . Inhibition of inositol phosphate second messenger formation by intracellular loop one of a human calcitonin receptor. Expression and mutational analysis of synthetic receptor genes . The Journal of Biological Chemistry . 269 . 45 . 28123–9 . November 1994 . 10.1016/S0021-9258(18)46903-7 . 7961748 . free .
• Kuestner RE, Elrod RD, Grant FJ, Hagen FS, Kuijper JL, Matthewes SL, O'Hara PJ, Sheppard PO, Stroop SD, Thompson DL . Cloning and characterization of an abundant subtype of the human calcitonin receptor . Molecular Pharmacology . 46 . 2 . 246–55 . August 1994 . 8078488 .
• Frendo JL, Pichaud F, Mourroux RD, Bouizar Z, Segond N, Moukhtar MS, Jullienne A . An isoform of the human calcitonin receptor is expressed in TT cells and in medullary carcinoma of the thyroid . FEBS Letters . 342 . 2 . 214–6 . April 1994 . 8143880 . 10.1016/0014-5793(94)80503-2 . 5709002 . free . 1994FEBSL.342..214F .
• Masi L, Becherini L, Gennari L, Colli E, Mansani R, Falchetti A, Cepollaro C, Gonnelli S, Tanini A, Brandi ML . Allelic variants of human calcitonin receptor: distribution and association with bone mass in postmenopausal Italian women . Biochemical and Biophysical Research Communications . 245 . 2 . 622–6 . April 1998 . 9571205 . 10.1006/bbrc.1998.8445 .
• Taboulet J, Frenkian M, Frendo JL, Feingold N, Jullienne A, de Vernejoul MC . Calcitonin receptor polymorphism is associated with a decreased fracture risk in post-menopausal women . Human Molecular Genetics . 7 . 13 . 2129–33 . December 1998 . 9817931 . 10.1093/hmg/7.13.2129 . free .
• Christopoulos G, Perry KJ, Morfis M, Tilakaratne N, Gao Y, Fraser NJ, Main MJ, Foord SM, Sexton PM . Multiple amylin receptors arise from receptor activity-modifying protein interaction with the calcitonin receptor gene product . Molecular Pharmacology . 56 . 1 . 235–42 . July 1999 . 10385705 . 10.1124/mol.56.1.235.
• Nishikawa T, Ishikawa H, Yamamoto S, Koshihara Y . A novel calcitonin receptor gene in human osteoclasts from normal bone marrow . FEBS Letters . 458 . 3 . 409–14 . September 1999 . 10570950 . 10.1016/S0014-5793(99)01176-X . 41350895 . free . 1999FEBSL.458..409N .
• Beaudreuil J, Taboulet J, Orcel P, Graulet AM, Denne MA, Baudoin C, Jullienne A, De Vernejoul MC . Calcitonin receptor mRNA in mononuclear leucocytes from postmenopausal women: decrease during osteoporosis and link to bone markers with specific isoform involvement . Bone . 27 . 1 . 161–8 . July 2000 . 10865224 . 10.1016/S8756-3282(00)00305-7 .
• Wada S, Yasuda S, Nagai T, Maeda T, Kitahama S, Suda S, Findlay DM, Iitaka M, Katayama S . Regulation of calcitonin receptor by glucocorticoid in human osteoclast-like cells prepared in vitro using receptor activator of nuclear factor-kappaB ligand and macrophage colony-stimulating factor . Endocrinology . 142 . 4 . 1471–8 . April 2001 . 11250927 . 10.1210/endo.142.4.8085 . free .
• Ogden CA, deCathelineau A, Hoffmann PR, Bratton D, Ghebrehiwet B, Fadok VA, Henson PM . C1q and mannose binding lectin engagement of cell surface calreticulin and CD91 initiates macropinocytosis and uptake of apoptotic cells . The Journal of Experimental Medicine . 194 . 6 . 781–95 . September 2001 . 11560994 . 2195958 . 10.1084/jem.194.6.781 .
• Nosaka Y, Tachi Y, Shimpuku H, Kawamura T, Ohura K . Association of calcitonin receptor gene polymorphism with early marginal bone loss around endosseous implants . The International Journal of Oral & Maxillofacial Implants . 17 . 1 . 38–43 . 2002 . 11858573 .
• Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, Wagner L, Shenmen CM, Schuler GD, Altschul SF, Zeeberg B, Buetow KH, Schaefer CF, Bhat NK, Hopkins RF, Jordan H, Moore T, Max SI, Wang J, Hsieh F, Diatchenko L, Marusina K, Farmer AA, Rubin GM, Hong L, Stapleton M, Soares MB, Bonaldo MF, Casavant TL, Scheetz TE, Brownstein MJ, Usdin TB, Toshiyuki S, Carninci P, Prange C, Raha SS, Loquellano NA, Peters GJ, Abramson RD, Mullahy SJ, Bosak SA, McEwan PJ, McKernan KJ, Malek JA, Gunaratne PH, Richards S, Worley KC, Hale S, Garcia AM, Gay LJ, Hulyk SW, Villalon DK, Muzny DM, Sodergren EJ, Lu X, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madan A, Young AC, Shevchenko Y, Bouffard GG, Blakesley RW, Touchman JW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Krzywinski MI, Skalska U, Smailus DE, Schnerch A, Schein JE, Jones SJ, Marra MA . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proceedings of the National Academy of Sciences of the United States of America . 99 . 26 . 16899–903 . December 2002 . 12477932 . 139241 . 10.1073/pnas.242603899 . 2002PNAS...9916899M . free .

External links

• Web site: Calcitonin Receptors . IUPHAR Database of Receptors and Ion Channels . International Union of Basic and Clinical Pharmacology . 2007-07-23 . 2016-03-03 . https://web.archive.org/web/20160303193951/http://www.iuphar-db.org/GPCR/ChapterMenuForward?chapterID=1358 . dead .