Genomes and Genes
Summary: Cell surface proteins that bind calcitonin and trigger intracellular changes which influence the behavior of cells. Calcitonin receptors outside the nervous system mediate the role of calcitonin in calcium homeostasis. The role of calcitonin receptors in the brain is not well understood.
- Hasdemir B, Bunnett N, Cottrell G. Hepatocyte growth factor-regulated tyrosine kinase substrate (HRS) mediates post-endocytic trafficking of protease-activated receptor 2 and calcitonin receptor-like receptor. J Biol Chem. 2007;282:29646-57 pubmed..The ultimate sorting decision to degradative or recycling pathways appears to occur downstream from HRS. ..
- Gujer R, Aldecoa A, Bühlmann N, Leuthäuser K, Muff R, Fischer J, et al. Mutations of the asparagine117 residue of a receptor activity-modifying protein 1-dependent human calcitonin gene-related peptide receptor result in selective loss of function. Biochemistry. 2001;40:5392-8 pubmed..Unlike Asn(60) and Asn(112), Asn(117) is normally not N-glycosylated, but essential for CGRP binding to the hCRLR-RAMP1 complex. ..
- Nicholson G, Horton M, Sexton P, D Santos C, Moseley J, Kemp B, et al. Calcitonin receptors of human osteoclastoma. Horm Metab Res. 1987;19:585-9 pubmed..The multinucleate giant cells (osteoclasts) of human osteoclastomas possess large number of CT receptors which exhibit the same binding kinetics and apparent Mr as those of other CT target cells. ..
- Cottrell G, Roosterman D, Marvizon J, Song B, Wick E, Pikios S, et al. Localization of calcitonin receptor-like receptor and receptor activity modifying protein 1 in enteric neurons, dorsal root ganglia, and the spinal cord of the rat. J Comp Neurol. 2005;490:239-55 pubmed
- Lee S, Goldring S, Lorenzo J. Expression of the calcitonin receptor in bone marrow cell cultures and in bone: a specific marker of the differentiated osteoclast that is regulated by calcitonin. Endocrinology. 1995;136:4572-81 pubmed..Both MNCs that formed in bone marrow cultures and isolated primary osteoclasts formed resorption pits on bone slices.(ABSTRACT TRUNCATED AT 400 WORDS) ..
- Pondel M. Calcitonin and calcitonin receptors: bone and beyond. Int J Exp Pathol. 2000;81:405-22 pubmed
- Hilairet S, Belanger C, Bertrand J, Laperriere A, Foord S, Bouvier M. Agonist-promoted internalization of a ternary complex between calcitonin receptor-like receptor, receptor activity-modifying protein 1 (RAMP1), and beta-arrestin. J Biol Chem. 2001;276:42182-90 pubmed..These results therefore indicate that although atypical by its heterodimeric composition and its targeting to the plasma membrane, the CGRP receptor shares endocytotic mechanisms that are common to most classical 7TM receptors. ..
- Sexton P, Findlay D, Martin T. Calcitonin. Curr Med Chem. 1999;6:1067-93 pubmed..Finally, current therapeutic use is reviewed, and the potential for expanded use that may come with advances in delivery of peptides or CT mimetics. ..
- Christopoulos G, Perry K, Morfis M, Tilakaratne N, Gao Y, Fraser N, et al. Multiple amylin receptors arise from receptor activity-modifying protein interaction with the calcitonin receptor gene product. Mol Pharmacol. 1999;56:235-42 pubmed
- Sondergaard B, Wulf H, Henriksen K, Schaller S, Oestergaard S, Qvist P, et al. Calcitonin directly attenuates collagen type II degradation by inhibition of matrix metalloproteinase expression and activity in articular chondrocytes. Osteoarthritis Cartilage. 2006;14:759-68 pubmed..001) decrease in CTX-II levels. These results are the first evidence of calcitonin receptor expression on articular chondrocytes and that the chondroprotective effects of calcitonin might involve the inhibition of MMP expression. ..
- Fukada S, Uezumi A, Ikemoto M, Masuda S, Segawa M, Tanimura N, et al. Molecular signature of quiescent satellite cells in adult skeletal muscle. Stem Cells. 2007;25:2448-59 pubmed..Our data provide roles of CTR in quiescent satellite cells and a solid scaffold to further dissect molecular regulation of satellite cells. Disclosure of potential conflicts of interest is found at the end of this article...
- Kuestner R, Elrod R, Grant F, Hagen F, Kuijper J, Matthewes S, et al. Cloning and characterization of an abundant subtype of the human calcitonin receptor. Mol Pharmacol. 1994;46:246-55 pubmed..Lastly, by using a human/rodent somatic cell hybrid panel and in situ hybridization, we localized the human calcitonin receptor gene to chromosome 7. ..
- Mandelin J, Liljeström M, Li T, Ainola M, Hukkanen M, Salo J, et al. Pseudosynovial fluid from loosened total hip prosthesis induces osteoclast formation. J Biomed Mater Res B Appl Biomater. 2005;74:582-8 pubmed..It is thus concluded that suppression of RANKL activity may be beneficial in terms of increasing the lifetime of total hip prostheses. ..
- Njuki F, Nicholl C, Howard A, Mak J, Barnes P, Girgis S, et al. A new calcitonin-receptor-like sequence in rat pulmonary blood vessels. Clin Sci (Lond). 1993;85:385-8 pubmed..Both have binding activity in the lung and are potent vasodilators. The gene represented by this sequence may therefore play an important role in the maintenance of vascular tone. ..
- Ittner L, Koller D, Muff R, Fischer J, Born W. The N-terminal extracellular domain 23-60 of the calcitonin receptor-like receptor in chimeras with the parathyroid hormone receptor mediates association with receptor activity-modifying protein 1. Biochemistry. 2005;44:5749-54 pubmed..In conclusion, structural elements in the extreme N-terminus of the CLR between amino acids 23-60 are required and sufficient for CLR/RAMP1 cotransport to the plasma membrane and heterodimerization. ..
- McLatchie L, Fraser N, Main M, Wise A, Brown J, Thompson N, et al. RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor. Nature. 1998;393:333-9 pubmed..RAMP1 presents the receptor at the cell surface as a mature glycoprotein and a CGRP receptor. RAMP2-transported receptors are core-glycosylated and are adrenomedullin receptors. ..
- Kusano S, Kukimoto Niino M, Akasaka R, Toyama M, Terada T, Shirouzu M, et al. Crystal structure of the human receptor activity-modifying protein 1 extracellular domain. Protein Sci. 2008;17:1907-14 pubmed publisher..These results suggest that the hydrophobic patch participates in the interaction with CRLR and the formation of the ligand-binding pocket when it forms the CRLR.RAMP1 heterodimer. ..
- Muff R, Bühlmann N, Fischer J, Born W. An amylin receptor is revealed following co-transfection of a calcitonin receptor with receptor activity modifying proteins-1 or -3. Endocrinology. 1999;140:2924-7 pubmed..In conclusion, RAMP1 and -3 decrease calcitonin receptor expression in RAEC transfected with hCTR2 encoding cDNA and simultanously reveal an amylin receptor. ..
- Banerjee S, Evanson J, Harris E, Lowe S, Thomasson K, Porter J. Identification of specific calcitonin-like receptor residues important for calcitonin gene-related peptide high affinity binding. BMC Pharmacol. 2006;6:9 pubmed
- Conner A, Hay D, Simms J, Howitt S, Schindler M, Smith D, et al. A key role for transmembrane prolines in calcitonin receptor-like receptor agonist binding and signalling: implications for family B G-protein-coupled receptors. Mol Pharmacol. 2005;67:20-31 pubmed..P321A-I325P, predicted to restore this conformation, showed wild-type activation. Modeling can also rationalize the effects of transmembrane proline mutants previously reported for another family B GPCR, the VPAC(1) receptor. ..
- Cottrell G, Padilla B, Pikios S, Roosterman D, Steinhoff M, Grady E, et al. Post-endocytic sorting of calcitonin receptor-like receptor and receptor activity-modifying protein 1. J Biol Chem. 2007;282:12260-71 pubmed..After sustained stimulation, CLR and RAMP1 traffic from endosomes to lysosomes by ubiquitin-independent mechanisms, where they are degraded at different rates. ..
- Simms J, Hay D, Bailey R, Konycheva G, Bailey G, Wheatley M, et al. Structure-function analysis of RAMP1 by alanine mutagenesis. Biochemistry. 2009;48:198-205 pubmed publisher..The data are consistent with a CLR recognition site particularly involving Y66 and H97, with lesser roles for adjacent residues in helix 3. L69 and T73 may contribute to a CGRP recognition site in helix 2 also involving nearby residues. ..
- Nakazawa I, Nakajima T, Harada H, Ishigami T, Umemura S, Emi M. Human calcitonin receptor-like receptor for adrenomedullin: genomic structure, eight single-nucleotide polymorphisms, and haplotype analysis. J Hum Genet. 2001;46:132-6 pubmed..The data establish a basis for investigations to detect molecular variants in the ADM receptor that might alter control of blood pressure and confer on individuals a predisposition to essential hypertension. ..
- Anusaksathien O, Laplace C, Li X, Ren Y, Peng L, Goldring S, et al. Tissue-specific and ubiquitous promoters direct the expression of alternatively spliced transcripts from the calcitonin receptor gene. J Biol Chem. 2001;276:22663-74 pubmed..These transfection data confirm the osteoclast specificity of promoter P3 and provide the first evidence that the CTR gene is regulated in a tissue-specific manner by alternative promoter utilization. ..
- Christopoulos A, Christopoulos G, Morfis M, Udawela M, Laburthe M, Couvineau A, et al. Novel receptor partners and function of receptor activity-modifying proteins. J Biol Chem. 2003;278:3293-7 pubmed..Our findings identify a new functional consequence of RAMP-receptor interaction, suggesting that RAMPs play a more general role in modulating cell signaling through other GPCRs than is currently appreciated. ..
- Lin Z, Pavlos N, Cake M, Wood D, Xu J, Zheng M. Evidence that human cartilage and chondrocytes do not express calcitonin receptor. Osteoarthritis Cartilage. 2008;16:450-7 pubmed..Furthermore, sCT does not appear to have direct effects on human chondrocytes. We propose that the chondroprotective effect of CT observed in vivo may be indirect via its impact on subchondral bone resorptive activity of osteoclasts. ..
- Hilairet S, Foord S, Marshall F, Bouvier M. Protein-protein interaction and not glycosylation determines the binding selectivity of heterodimers between the calcitonin receptor-like receptor and the receptor activity-modifying proteins. J Biol Chem. 2001;276:29575-81 pubmed..Overall, the data indicate that direct protein-protein interactions dictate the pharmacological properties of the CRLR-RAMP complexes. ..
- Dong M, Pinon D, Cox R, Miller L. Importance of the amino terminus in secretin family G protein-coupled receptors. Intrinsic photoaffinity labeling establishes initial docking constraints for the calcitonin receptor. J Biol Chem. 2004;279:1167-75 pubmed..deglycosylation, specific chemical and enzymatic cleavage, and sequencing of labeled wild type and mutant calcitonin receptors identified the sites of labeling for the position 16 and 26 probes as receptor residues Phe137 and Thr30, ..
- Martin T, Sims N. Osteoclast-derived activity in the coupling of bone formation to resorption. Trends Mol Med. 2005;11:76-81 pubmed..We argue that osteoclasts contribute in important ways to the transiently activated osteoclast, and stimulate osteoblast lineage cells to begin replacing the resorbed bone in each BMU. ..
- Blower P, Puncher M, Kettle A, George S, Dorsch S, Leak A, et al. Iodine-123 salmon calcitonin, an imaging agent for calcitonin receptors: synthesis, biodistribution, metabolism and dosimetry in humans. Eur J Nucl Med. 1998;25:101-8 pubmed..In summary, [123I]diiodotyrosyl22-SCT binds to calcitonin receptors and can image sites of Paget's disease but its imaging potential is not optimal because of rapid breakdown ..
- Katafuchi T, Kikumoto K, Hamano K, Kangawa K, Matsuo H, Minamino N. Calcitonin receptor-stimulating peptide, a new member of the calcitonin gene-related peptide family. Its isolation from porcine brain, structure, tissue distribution, and biological activity. J Biol Chem. 2003;278:12046-54 pubmed..These unique properties indicate that CRSP is not a porcine counterpart of betaCGRP and probably elicits its biological effects via the calcitonin receptor. ..
- Heroux M, Hogue M, Lemieux S, Bouvier M. Functional calcitonin gene-related peptide receptors are formed by the asymmetric assembly of a calcitonin receptor-like receptor homo-oligomer and a monomer of receptor activity-modifying protein-1. J Biol Chem. 2007;282:31610-20 pubmed
- Hirose T, Totsune K, Mori N, Mori T, Morimoto R, Metoki H, et al. Expression of adrenomedullin 2/intermedin, a possible reno-protective peptide, is decreased in the kidneys of rats with hypertension or renal failure. Am J Physiol Renal Physiol. 2010;299:F128-34 pubmed publisher..Given the organ-protective effects of AM2/IMD, the downregulation of AM2/IMD as an endogenous regulatory peptide may have a role in the progression of renal impairment. ..
- Hasbak P, Saetrum Opgaard O, Eskesen K, Schifter S, Arendrup H, Longmore J, et al. Investigation of CGRP receptors and peptide pharmacology in human coronary arteries. Characterization with a nonpeptide antagonist. J Pharmacol Exp Ther. 2003;304:326-33 pubmed..Compound 1 acted as a nonpeptide antagonist at the CGRP1 receptor and could thus become a tool for the study of CGRP-mediated functional responses in human tissue. ..
- Charopoulos I, Trovas G, Stathopoulou M, Kyriazopoulos P, Galanos A, Dedoussis G, et al. Lack of association between vitamin D and calcitonin receptor gene polymorphisms and forearm bone values of young Greek males. J Musculoskelet Neuronal Interact. 2008;8:196-203 pubmed..Findings did not change after adjusting for demographic characteristics. The BsmI and AluI polymorphisms are not related to the forearm bone values either reflecting mass or geometrical variables in this male population. ..
- Nagoshi Y, Kuwasako K, Cao Y, Imamura T, Kitamura K, Eto T. Tumor necrosis factor-alpha downregulates adrenomedullin receptors in human coronary artery smooth muscle cells. Peptides. 2004;25:1115-21 pubmed..The suppression of these three mRNAs was unaffected by inhibiting NOS, protein kinase G, protein kinase A, superoxide formation or NF-kappaB activation. ..
- Lindfors P, Lindahl M, Rossi J, Saarma M, Airaksinen M. Ablation of persephin receptor glial cell line-derived neurotrophic factor family receptor alpha4 impairs thyroid calcitonin production in young mice. Endocrinology. 2006;147:2237-44 pubmed..In conclusion, this study indicates a novel role for endogenous GFRalpha4 signaling in regulating calcitonin production in thyroid C cells of young mice. ..
- Lerner U. Deletions of genes encoding calcitonin/alpha-CGRP, amylin and calcitonin receptor have given new and unexpected insights into the function of calcitonin receptors and calcitonin receptor-like receptors in bone. J Musculoskelet Neuronal Interact. 2006;6:87-95 pubmed..Thus, our understanding of the role of the CT family of peptides has been changed dramatically and much more data have to be gained before we fully understand the roles these peptides have in bone biology. ..
- Frayon S, Cueille C, Gnidehou S, De Vernejoul M, Garel J. Dexamethasone increases RAMP1 and CRLR mRNA expressions in human vascular smooth muscle cells. Biochem Biophys Res Commun. 2000;270:1063-7 pubmed..Thus, we suggest that, in vivo, glucocorticoids are involved in the expression of CGRP receptors by human coronary VSMC. ..
- Gouron R, Petit L, Boudot C, Six I, Brazier M, Kamel S, et al. Osteoclasts and their precursors are present in the induced-membrane during bone reconstruction using the Masquelet technique. J Tissue Eng Regen Med. 2017;11:382-389 pubmed publisher..Copyright © 2014 John Wiley & Sons, Ltd. ..
- Koth C, Abdul Manan N, Lepre C, Connolly P, Yoo S, Mohanty A, et al. Refolding and characterization of a soluble ectodomain complex of the calcitonin gene-related peptide receptor. Biochemistry. 2010;49:1862-72 pubmed publisher..02 muM), as well as N-terminally truncated peptides and peptide analogues (140 nM to 1.62 microM) was observed. ..
- Komine M, Kukita A, Kukita T, Ogata Y, Hotokebuchi T, Kohashi O. Tumor necrosis factor-alpha cooperates with receptor activator of nuclear factor kappaB ligand in generation of osteoclasts in stromal cell-depleted rat bone marrow cell culture. Bone. 2001;28:474-83 pubmed..This formation was abolished by the addition of human osteoprotegerin (hOPG). These results suggest that cooperation of TNF-alpha and RANKL is important for osteoclastogenesis. ..
- Nishikimi T. Adrenomedullin in the kidney-renal physiological and pathophysiological roles. Curr Med Chem. 2007;14:1689-99 pubmed..This review describes the biochemistry, physiology, and circulating levels of AM and also discusses what is known about the pathophysiological role of AM in renal disease. ..
- Giuliani S, Wimalawansa S, Maggi C. Involvement of multiple receptors in the biological effects of calcitonin gene-related peptide and amylin in rat and guinea-pig preparations. Br J Pharmacol. 1992;107:510-4 pubmed..This latter type of receptor could be entirely responsible for the action of the agonists in the guinea-pig urinary bladder. ..
- Stroop S, Nakamuta H, Kuestner R, Moore E, Epand R. Determinants for calcitonin analog interaction with the calcitonin receptor N-terminus and transmembrane-loop regions. Endocrinology. 1996;137:4752-6 pubmed..Thus, unique requirements exist for CT interaction at the receptor N-terminus relative to the receptor transmembrane loop region, yet there is significant overlap in the hormone determinants that facilitate these interactions. ..
- Gillespie M, Thomas R, Pu Z, Zhou H, Martin T, Findlay D. Calcitonin receptors, bone sialoprotein and osteopontin are expressed in primary breast cancers. Int J Cancer. 1997;73:812-5 pubmed..Expression of CTR, BSP and OPN may prove to be a useful marker for breast cancers, and their role in the homing of breast cancer cells to bone remains to be investigated. ..
- Cui Y, Zhao X, Mei L, Pei J, Wang S, Shao Y, et al. Osteon Myospalacem Baileyi attenuates osteoclast differentiation through RANKL induced NFAT pathways. J Ethnopharmacol. 2018;213:65-71 pubmed publisher..These data suggest that ET4 might be a useful alternative therapy in preventing or treating osteolytic diseases. ..
- Hjuler S, Gydesen S, Andreassen K, Pedersen S, Hellgren L, Karsdal M, et al. The dual amylin- and calcitonin-receptor agonist KBP-042 increases insulin sensitivity and induces weight loss in rats with obesity. Obesity (Silver Spring). 2016;24:1712-22 pubmed publisher..The study indicates that KBP-042 combines two highly relevant features, namely weight loss and insulin sensitivity, and is thus an excellent candidate for chronic treatment of obesity and insulin resistance. ..
- Totsune K, Takahashi K, Mackenzie H, Arihara Z, Satoh F, Sone M, et al. Adrenomedullin and its receptor complexes in remnant kidneys of rats with renal mass ablation: decreased expression of calcitonin receptor-like receptor and receptor-activity modifying protein-3. Peptides. 2001;22:1933-7 pubmed..The present study showed that expression of mRNAs encoding AM, RAMP2, RAMP3 and CRLR were differentially regulated in remnant kidneys of rats with renal mass ablation. ..
- Makino Y, Shibata K, Makino I, Kangawa K, Kawarabayashi T. Alteration of the adrenomedullin receptor components gene expression associated with the blood pressure in pregnancy-induced hypertension. J Clin Endocrinol Metab. 2001;86:5079-82 pubmed..These findings suggested that the reduced expression of adrenomedullin receptor component in umbilical artery and uterus may have some role in PIH. ..
- Morfis M, Christopoulos A, Sexton P. RAMPs: 5 years on, where to now?. Trends Pharmacol Sci. 2003;24:596-601 pubmed..In this article, we review recent developments, including the identification of new receptor partners and novel roles for RAMPs. ..
- Fukai N, Yoshimoto T, Sugiyama T, Ozawa N, Sato R, Shichiri M, et al. Concomitant expression of adrenomedullin and its receptor components in rat adipose tissues. Am J Physiol Endocrinol Metab. 2005;288:E56-62 pubmed..These data suggest that AM may act as a new member of adipokines, although its functional role, as well as its pathophysiological significance in obesity, remains to be determined. ..
- Mangashetti L, Khapli S, Wani M. IL-4 inhibits bone-resorbing activity of mature osteoclasts by affecting NF-kappa B and Ca2+ signaling. J Immunol. 2005;175:917-25 pubmed..Furthermore, IL-4 inhibits bone resorption and actin ring formation by human mature osteoclasts. Thus, we reveal that IL-4 acts directly on mature osteoclasts and inhibits bone resorption by inhibiting NF-kappaB and Ca(2+) signaling. ..