{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T02:09:09Z","timestamp":1790302149591,"version":"4.1.0"},"reference-count":170,"publisher":"Bioscientifica","issue":"1","content-domain":{"domain":["jme.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:p>\n                    The calcium-sensing receptor (CASR) is a class C G-protein-coupled receptor (GPCR) that detects extracellular calcium concentrations, and modulates parathyroid hormone secretion and urinary calcium excretion to maintain calcium homeostasis. The CASR utilises multiple heterotrimeric G-proteins to mediate signalling effects including activation of intracellular calcium release; mitogen-activated protein kinase (MAPK) pathways; membrane ruffling; and inhibition of cAMP production. By studying germline mutations in the CASR and proteins within its signalling pathway that cause hyper- and hypocalcaemic disorders, novel mechanisms governing GPCR signalling and trafficking have been elucidated. This review focusses on two recently described pathways that provide novel insights into CASR signalling and trafficking mechanisms. The first, identified by studying a CASR gain-of-function mutation that causes autosomal dominant hypocalcaemia (ADH), demonstrated a structural motif located between the third transmembrane domain and the second extracellular loop of the CASR that mediates biased signalling by activating a novel \u03b2-arrestin-mediated G-protein-independent pathway. The second, in which the mechanism by which adaptor protein-2 \u03c3-subunit (AP2\u03c3) mutations cause familial hypocalciuric hypercalcaemia (FHH) was investigated, demonstrated that AP2\u03c3 mutations impair CASR internalisation and reduce multiple CASR-mediated signalling pathways. Furthermore, these studies showed that the CASR can signal from the cell surface using multiple G-protein pathways, whilst sustained signalling is mediated only by the G\n                    <jats:sub>q\/11<\/jats:sub>\n                    pathway. Thus, studies of FHH- and ADH-associated mutations have revealed novel steps by which CASR mediates signalling and compartmental bias, and these pathways could provide new targets for therapies for patients with calcaemic disorders.\n                  <\/jats:p>","DOI":"10.1530\/jme-18-0049","type":"journal-article","created":{"date-parts":[[2018,3,29]],"date-time":"2018-03-29T12:50:18Z","timestamp":1522327818000},"page":"R1-R12","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-6","source":"Crossref","is-referenced-by-count":28,"title":["Insights into calcium-sensing receptor trafficking and biased signalling by studies of calcium homeostasis"],"prefix":"10.1530","volume":"61","author":[{"given":"Caroline M","family":"Gorvin","sequence":"first","affiliation":[{"name":"1Institute of Metabolism and Systems Research (IMSR), University of Birmingham, Birmingham, UK"},{"name":"2Centre for Endocrinology, Diabetes and Metabolism (CEDAM), Birmingham Health Partners, Birmingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"ref1521","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1242\/jcs.00289","article-title":"Real-time analysis of clathrin-mediated endocytosis during cell migration","volume":"116","year":"2003","journal-title":"Journal of Cell Science"},{"key":"ref1691","doi-asserted-by":"crossref","first-page":"e1600241","DOI":"10.1126\/sciadv.1600241","article-title":"Structural basis for regulation of human calcium-sensing receptor by magnesium ions and an unexpected tryptophan derivative co-agonist","volume":"2","year":"2016","journal-title":"Science Advances"},{"key":"ref321","doi-asserted-by":"crossref","first-page":"10060","DOI":"10.1074\/jbc.M312039200","article-title":"Calcium-sensing receptor-mediated ERK1\/2 activation requires Galphai2 coupling and dynamin-independent receptor internalization","volume":"279","year":"2004","journal-title":"Journal of Biological Chemistry"},{"key":"ref1071","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1016\/j.celrep.2017.12.089","article-title":"AP2\u03c3 mutations impair calcium-sensing receptor trafficking and signaling revealing an endosomal pathway that spatially directs G-protein selectivity","volume":"22","year":"2018b","journal-title":"Cell Reports"},{"key":"ref631","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1210\/me.2004-0450","article-title":"Beta-arrestin- and G protein receptor kinase-mediated calcium-sensing receptor desensitization","volume":"19","year":"2005","journal-title":"Molecular Endocrinology"},{"key":"ref1671","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1073\/pnas.1205756110","article-title":"Noncanonical GPCR signaling arising from a PTH receptor-arrestin-Gbetagamma complex","volume":"110","year":"2013","journal-title":"PNAS"},{"key":"ref341","doi-asserted-by":"crossref","first-page":"5113","DOI":"10.1074\/jbc.M413403200","article-title":"A region in the seven-transmembrane domain of the human Ca2+ receptor critical for response to Ca2+","volume":"280","year":"2005","journal-title":"Journal of Biological Chemistry"},{"key":"ref371","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/B978-0-12-385952-5.00007-5","article-title":"Regulation of stability and trafficking of calcium-sensing receptors by pharmacologic chaperones","volume":"62","year":"2011","journal-title":"Advances in Pharmacology"},{"key":"ref461","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.neuron.2011.05.036","article-title":"Endocytosis promotes rapid dopaminergic signaling","volume":"71","year":"2011","journal-title":"Neuron"},{"key":"ref1361","doi-asserted-by":"crossref","first-page":"2532","DOI":"10.1056\/NEJMc1300278","article-title":"Germline mutations affecting Galpha11 in hypoparathyroidism","volume":"368","year":"2013","journal-title":"New England Journal of Medicine"},{"key":"ref851","doi-asserted-by":"crossref","first-page":"29171","DOI":"10.1074\/jbc.M103747200","article-title":"Activation of the beta 2-adrenergic receptor involves disruption of an ionic lock between the cytoplasmic ends of transmembrane segments 3 and 6","volume":"276","year":"2001","journal-title":"Journal of Biological Chemistry"},{"key":"ref1111","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.beem.2013.04.007","article-title":"Calcium-sensing receptor (CaSR) mutations and disorders of calcium, electrolyte and water metabolism","volume":"27","year":"2013","journal-title":"Best Practice and Research: Clinical Endocrinology and Metabolism"},{"key":"ref651","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1002\/jbmr.2797","article-title":"Identification of a G-protein subunit-alpha11 gain-of-function mutation, Val340Met, in a family with autosomal dominant hypocalcemia type 2 (ADH2)","volume":"31","year":"2016","journal-title":"Journal of Bone and Mineral Research"},{"key":"ref1471","doi-asserted-by":"crossref","first-page":"3830","DOI":"10.1210\/en.2002-220240","article-title":"Calcium-sensing receptor activation of Rho involves filamin and Rho-guanine nucleotide exchange factor","volume":"143","year":"2002","journal-title":"Endocrinology"},{"key":"ref301","doi-asserted-by":"crossref","first-page":"34880","DOI":"10.1074\/jbc.M100784200","article-title":"Filamin-A binds to the carboxyl-terminal tail of the calcium-sensing receptor, an interaction that participates in CaR-mediated activation of mitogen-activated protein kinase","volume":"276","year":"2001","journal-title":"Journal of Biological Chemistry"},{"key":"ref381","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1038\/nature12000","article-title":"Conformational biosensors reveal GPCR signalling from endosomes","volume":"495","year":"2013","journal-title":"Nature"},{"key":"ref531","doi-asserted-by":"crossref","first-page":"7254","DOI":"10.1074\/jbc.M307191200","article-title":"Homology modeling of the transmembrane domain of the human calcium sensing receptor and localization of an allosteric binding site","volume":"279","year":"2004","journal-title":"Journal of Biological Chemistry"},{"key":"ref351","doi-asserted-by":"crossref","first-page":"21558","DOI":"10.1074\/jbc.M603682200","article-title":"A missense mutation in the seven-transmembrane domain of the human Ca2+ receptor converts a negative allosteric modulator into a positive allosteric modulator","volume":"281","year":"2006","journal-title":"Journal of Biological Chemistry"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1210\/me.2011-1370","article-title":"Minireview: the intimate link between calcium sensing receptor trafficking and signaling: implications for disorders of calcium homeostasis","volume":"26","year":"2012","journal-title":"Molecular Endocrinology"},{"key":"ref181","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1002\/jbmr.2778","article-title":"A G-protein subunit-alpha11 loss-of-function mutation, Thr54Met, causes familial hypocalciuric hypercalcemia type 2 (FHH2)","volume":"31","year":"2016","journal-title":"Journal of Bone and Mineral Research"},{"key":"ref171","doi-asserted-by":"crossref","first-page":"e13662","DOI":"10.7554\/eLife.13662","article-title":"Structural mechanism of ligand activation in human calcium-sensing receptor","volume":"5","year":"2016","journal-title":"Elife"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1152\/physrev.1991.71.2.371","article-title":"Extracellular Ca2+ sensing, regulation of parathyroid cell function, and role of Ca2+ and other ions as extracellular (first) messengers","volume":"71","year":"1991","journal-title":"Physiological Reviews"},{"key":"ref101","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.beem.2013.05.010","article-title":"Calcium-sensing receptor (CaSR): pharmacological properties and signaling pathways","volume":"27","year":"2013","journal-title":"Best Practice and Research: Clinical Endocrinology and Metabolism"},{"key":"ref681","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/nature06325","article-title":"Crystal structure of the human beta2 adrenergic G-protein-coupled receptor","volume":"450","year":"2007","journal-title":"Nature"},{"key":"ref1251","doi-asserted-by":"crossref","first-page":"3960","DOI":"10.1074\/jbc.M113.526350","article-title":"Spatially restricted G protein-coupled receptor activity via divergent endocytic compartments","volume":"289","year":"2014","journal-title":"Journal of Biological Chemistry"},{"key":"ref1441","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.1172\/JCI118987","article-title":"Functional characterization of calcium-sensing receptor mutations expressed in human embryonic kidney cells","volume":"98","year":"1996a","journal-title":"Journal of Clinical Investigation"},{"key":"ref1461","doi-asserted-by":"crossref","first-page":"18990","DOI":"10.1074\/jbc.M400724200","article-title":"Positive and negative allosteric modulators of the Ca2+-sensing receptor interact within overlapping but not identical binding sites in the transmembrane domain","volume":"279","year":"2004","journal-title":"Journal of Biological Chemistry"},{"key":"ref991","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1210\/jcem-72-3-541","article-title":"Plasma intact parathyroid hormone (PTH) and PTH-related peptide in familial benign hypercalcemia: greater responsiveness to endogenous PTH than in primary hyperparathyroidism","volume":"72","year":"1991","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"ref1031","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1002\/jbmr.2778","article-title":"A G-protein subunit-alpha11 loss-of-function mutation, Thr54Met, causes familial hypocalciuric hypercalcemia type 2 (FHH2)","volume":"31","year":"2016","journal-title":"Journal of Bone and Mineral Research"},{"key":"ref1631","doi-asserted-by":"crossref","first-page":"2259","DOI":"10.1097\/01.ASN.0000025781.16723.68","article-title":"Functional characterization of a calcium-sensing receptor mutation in severe autosomal dominant hypocalcemia with a Bartter-like syndrome","volume":"13","year":"2002","journal-title":"Journal of the American Society of Nephrology"},{"key":"ref1301","doi-asserted-by":"crossref","first-page":"a016725","DOI":"10.1101\/cshperspect.a016725","article-title":"Molecular structure, function, and dynamics of clathrin-mediated membrane traffic","volume":"6","year":"2014","journal-title":"Cold Spring Harbor Perspectives in Biology"},{"key":"ref901","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1038\/366575a0","article-title":"Cloning and characterization of an extracellular Ca(2+)-sensing receptor from bovine parathyroid","volume":"366","year":"1993","journal-title":"Nature"},{"key":"ref1581","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1038\/nature09795","article-title":"The structural basis of agonist-induced activation in constitutively active rhodopsin","volume":"471","year":"2011","journal-title":"Nature"},{"key":"ref1311","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.neuron.2011.05.036","article-title":"Endocytosis promotes rapid dopaminergic signaling","volume":"71","year":"2011","journal-title":"Neuron"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"4709","DOI":"10.1242\/jcs.02598","article-title":"Receptor-activity-modifying proteins are required for forward trafficking of the calcium-sensing receptor to the plasma membrane","volume":"118","year":"2005","journal-title":"Journal of Cell Science"},{"key":"ref1331","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1210\/en.2012-1887","article-title":"Impact of clinically relevant mutations on the pharmacoregulation and signaling bias of the calcium-sensing receptor by positive and negative allosteric modulators","volume":"154","year":"2013","journal-title":"Endocrinology"},{"key":"ref121","doi-asserted-by":"crossref","first-page":"27849","DOI":"10.1074\/jbc.M112.445098","article-title":"Noncanonical control of vasopressin receptor type 2 signaling by retromer and arrestin","volume":"288","year":"2013","journal-title":"Journal of Biological Chemistry"},{"key":"ref1351","doi-asserted-by":"crossref","first-page":"2398","DOI":"10.1210\/en.2006-1035","article-title":"Functional desensitization of the extracellular calcium-sensing receptor is regulated via distinct mechanisms: role of G protein-coupled receptor kinases, protein kinase C and beta-arrestins","volume":"148","year":"2007","journal-title":"Endocrinology"},{"key":"ref1091","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1210\/me.2012-1232","article-title":"Calcium signaling regulates trafficking of familial hypocalciuric hypercalcemia (FHH) mutants of the calcium sensing receptor","volume":"26","year":"2012","journal-title":"Molecular Endocrinology"},{"key":"ref1101","doi-asserted-by":"crossref","first-page":"e0136702","DOI":"10.1371\/journal.pone.0136702","article-title":"14-3-3 proteins buffer intracellular calcium sensing receptors to constrain signaling","volume":"10","year":"2015","journal-title":"PLoS ONE"},{"key":"ref611","doi-asserted-by":"crossref","first-page":"18990","DOI":"10.1074\/jbc.M400724200","article-title":"Positive and negative allosteric modulators of the Ca2+-sensing receptor interact within overlapping but not identical binding sites in the transmembrane domain","volume":"279","year":"2004","journal-title":"Journal of Biological Chemistry"},{"key":"ref501","doi-asserted-by":"crossref","first-page":"2398","DOI":"10.1210\/en.2006-1035","article-title":"Functional desensitization of the extracellular calcium-sensing receptor is regulated via distinct mechanisms: role of G protein-coupled receptor kinases, protein kinase C and beta-arrestins","volume":"148","year":"2007","journal-title":"Endocrinology"},{"key":"ref201","first-page":"e91103","article-title":"Galpha11 mutation in mice causes hypocalcemia rectifiable by calcilytic therapy","volume":"2","year":"2017b","journal-title":"JCI Insight"},{"key":"ref1131","doi-asserted-by":"crossref","first-page":"5079","DOI":"10.1093\/hmg\/ddv226","article-title":"Adaptor protein-2 sigma subunit mutations causing familial hypocalciuric hypercalcaemia type 3 (FHH3) demonstrate genotype-phenotype correlations, codon bias and dominant-negative effects","volume":"24","year":"2015","journal-title":"Human Molecular Genetics"},{"key":"ref691","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1152\/ajprenal.00608.2009","article-title":"RiccardiDBrownEM and pathophysiology of the calcium - sensing receptor in the kidney of https org","year":"2010","journal-title":"Physiology American Journal Physiology Renal Physiology"},{"key":"ref1481","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1210\/me.2004-0450","article-title":"Beta-arrestin- and G protein receptor kinase-mediated calcium-sensing receptor desensitization","volume":"19","year":"2005","journal-title":"Molecular Endocrinology"},{"key":"ref571","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1007\/s00431-008-0794-y","article-title":"Unusually severe phenotype of neonatal primary hyperparathyroidism due to a heterozygous inactivating mutation in the CASR gene","volume":"168","year":"2009","journal-title":"European Journal of Pediatrics"},{"key":"ref1591","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1152\/ajpheart.00373.2010","article-title":"Calcium - sensing receptor : a sensor and mediator of ischemic preconditioning in the heart of and https org","author":"SunJMurphyE","year":"2010","journal-title":"American Journal Physiology Heart Circulatory Physiology"},{"key":"ref1181","doi-asserted-by":"crossref","first-page":"46622","DOI":"10.1074\/jbc.M207100200","article-title":"Identification of acidic residues in the extracellular loops of the seven-transmembrane domain of the human Ca2+ receptor critical for response to Ca2+ and a positive allosteric modulator","volume":"277","year":"2002","journal-title":"Journal of Biological Chemistry"},{"key":"ref71","doi-asserted-by":"crossref","first-page":"25030","DOI":"10.1074\/jbc.M700924200","article-title":"Complex formation with the Type B gamma-aminobutyric acid receptor affects the expression and signal transduction of the extracellular calcium-sensing receptor. Studies with HEK-293 cells and neurons","volume":"282","year":"2007","journal-title":"Journal of Biological Chemistry"},{"key":"ref1531","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/nature06325","article-title":"Crystal structure of the human beta2 adrenergic G-protein-coupled receptor","volume":"450","year":"2007","journal-title":"Nature"},{"key":"ref1051","first-page":"e91103","article-title":"Galpha11 mutation in mice causes hypocalcemia rectifiable by calcilytic therapy","volume":"2","year":"2017b","journal-title":"JCI Insight"},{"key":"ref701","doi-asserted-by":"crossref","first-page":"10156","DOI":"10.1038\/ncomms10156","article-title":"The experimental power of FR900359 to study Gq-regulated biological processes","volume":"6","year":"2015","journal-title":"Nature Communications"},{"key":"ref671","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1242\/jcs.00289","article-title":"Real-time analysis of clathrin-mediated endocytosis during cell migration","volume":"116","year":"2003","journal-title":"Journal of Cell Science"},{"key":"ref1621","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1002\/ajmg.a.30403","article-title":"A novel mutation (E767K) in the second extracellular loop of the calcium sensing receptor in a family with autosomal dominant hypocalcemia","volume":"132A","year":"2005","journal-title":"American Journal of Medical Genetics Part A"},{"key":"ref1151","doi-asserted-by":"crossref","first-page":"34880","DOI":"10.1074\/jbc.M100784200","article-title":"Filamin-A binds to the carboxyl-terminal tail of the calcium-sensing receptor, an interaction that participates in CaR-mediated activation of mitogen-activated protein kinase","volume":"276","year":"2001","journal-title":"Journal of Biological Chemistry"},{"key":"ref721","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1038\/nature13430","article-title":"Visualization of arrestin recruitment by a G-protein-coupled receptor","volume":"512","year":"2014","journal-title":"Nature"},{"key":"ref951","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.beem.2013.05.010","article-title":"Calcium-sensing receptor (CaSR): pharmacological properties and signaling pathways","volume":"27","year":"2013","journal-title":"Best Practice and Research: Clinical Endocrinology and Metabolism"},{"key":"ref161","doi-asserted-by":"crossref","first-page":"39053","DOI":"10.1074\/jbc.M105662200","article-title":"Heterodimerization of calcium sensing receptors with metabotropic glutamate receptors in neurons","volume":"276","year":"2001","journal-title":"Journal of Biological Chemistry"},{"key":"ref551","doi-asserted-by":"crossref","first-page":"2476","DOI":"10.1056\/NEJMoa1300253","article-title":"Mutations affecting G-protein subunit alpha11 in hypercalcemia and hypocalcemia","volume":"368","year":"2013a","journal-title":"New England Journal of Medicine"},{"key":"ref331","doi-asserted-by":"crossref","first-page":"46622","DOI":"10.1074\/jbc.M207100200","article-title":"Identification of acidic residues in the extracellular loops of the seven-transmembrane domain of the human Ca2+ receptor critical for response to Ca2+ and a positive allosteric modulator","volume":"277","year":"2002","journal-title":"Journal of Biological Chemistry"},{"key":"ref561","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/ng.2492","article-title":"Mutations in AP2S1 cause familial hypocalciuric hypercalcemia type 3","volume":"45","year":"2013b","journal-title":"Nature Genetics"},{"key":"ref1171","doi-asserted-by":"crossref","first-page":"10060","DOI":"10.1074\/jbc.M312039200","article-title":"Calcium-sensing receptor-mediated ERK1\/2 activation requires Galphai2 coupling and dynamin-independent receptor internalization","volume":"279","year":"2004","journal-title":"Journal of Biological Chemistry"},{"key":"ref661","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1016\/0092-8674(93)90617-Y","article-title":"Mutations in the human Ca(2+)-sensing receptor gene cause familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism","volume":"75","year":"1993","journal-title":"Cell"},{"key":"ref231","first-page":"ra78","article-title":"Agonist-driven maturation and plasma membrane insertion of calcium-sensing receptors dynamically control signal amplitude","volume":"4","year":"2011","journal-title":"Science Signaling"},{"key":"ref1241","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1016\/j.cell.2010.05.006","article-title":"A large-scale conformational change couples membrane recruitment to cargo binding in the AP2 clathrin adaptor complex","volume":"141","year":"2010","journal-title":"Cell"},{"key":"ref911","doi-asserted-by":"crossref","first-page":"e1000172","DOI":"10.1371\/journal.pbio.1000172","article-title":"Persistent cAMP-signals triggered by internalized G-protein-coupled receptors","volume":"7","year":"2009","journal-title":"PLoS Biology"},{"key":"ref941","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/S0092-8674(02)00735-3","article-title":"Molecular architecture and functional model of the endocytic AP2 complex","volume":"109","year":"2002","journal-title":"Cell"},{"key":"ref391","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1016\/j.cell.2010.05.006","article-title":"A large-scale conformational change couples membrane recruitment to cargo binding in the AP2 clathrin adaptor complex","volume":"141","year":"2010","journal-title":"Cell"},{"key":"ref111","doi-asserted-by":"crossref","first-page":"1916","DOI":"10.1210\/endo.138.5.5131","article-title":"N-linked glycosylation of the human Ca2+ receptor is essential for its expression at the cell surface","volume":"138","year":"1997","journal-title":"Endocrinology"},{"key":"ref581","doi-asserted-by":"crossref","first-page":"2683","DOI":"10.1172\/JCI118335","article-title":"Calcium-sensing receptor mutations in familial benign hypercalcemia and neonatal hyperparathyroidism","volume":"96","year":"1995","journal-title":"Journal of Clinical Investigation"},{"key":"ref641","doi-asserted-by":"crossref","first-page":"2200","DOI":"10.1093\/hmg\/ddl145","article-title":"Calcium-sensing receptor dimerizes in the endoplasmic reticulum: biochemical and biophysical characterization of CASR mutants retained intracellularly","volume":"15","year":"2006","journal-title":"Human Molecular Genetics"},{"key":"ref871","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1210\/me.2011-1370","article-title":"Minireview: the intimate link between calcium sensing receptor trafficking and signaling: implications for disorders of calcium homeostasis","volume":"26","year":"2012","journal-title":"Molecular Endocrinology"},{"key":"ref751","doi-asserted-by":"crossref","first-page":"47438","DOI":"10.1074\/jbc.M408846200","article-title":"A novel Galphaq\/11-selective inhibitor","volume":"279","year":"2004","journal-title":"Journal of Biological Chemistry"},{"key":"ref1061","doi-asserted-by":"crossref","first-page":"eaan3714","DOI":"10.1126\/scisignal.aan3714","article-title":"A calcium-sensing receptor mutation causing hypocalcemia disrupts a transmembrane salt bridge to activate \u03b2-arrestin biased signaling","volume":"11","year":"2018a","journal-title":"Sci Signal"},{"key":"ref1211","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1016\/j.febslet.2006.02.035","article-title":"Silencing of filamin A gene expression inhibits Ca2+-sensing receptor signaling","volume":"580","year":"2006","journal-title":"FEBS Letters"},{"key":"ref141","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1210\/jcem-72-3-541","article-title":"Plasma intact parathyroid hormone (PTH) and PTH-related peptide in familial benign hypercalcemia: greater responsiveness to endogenous PTH than in primary hyperparathyroidism","volume":"72","year":"1991","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"ref1001","doi-asserted-by":"crossref","first-page":"29712","DOI":"10.1074\/jbc.273.45.29712","article-title":"A carboxyl-terminal domain controls the cooperativity for extracellular Ca2+ activation of the human calcium sensing receptor. A study with receptor-green fluorescent protein fusions","volume":"273","year":"1998","journal-title":"Journal of Biological Chemistry"},{"key":"ref1401","doi-asserted-by":"crossref","first-page":"2476","DOI":"10.1056\/NEJMoa1300253","article-title":"Mutations affecting G-protein subunit alpha11 in hypercalcemia and hypocalcemia","volume":"368","year":"2013a","journal-title":"New England Journal of Medicine"},{"key":"ref741","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1152\/ajpheart.00373.2010","article-title":"Calcium - sensing receptor : a sensor and mediator of ischemic preconditioning in the heart of and https org","author":"SunJMurphyE","year":"2010","journal-title":"American Journal Physiology Heart Circulatory Physiology"},{"key":"ref1411","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/ng.2492","article-title":"Mutations in AP2S1 cause familial hypocalciuric hypercalcemia type 3","volume":"45","year":"2013b","journal-title":"Nature Genetics"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.beem.2013.03.003","article-title":"The calcium sensing receptor life cycle: trafficking, cell surface expression, and degradation","volume":"27","year":"2013","journal-title":"Best Practice and Research: Clinical Endocrinology and Metabolism"},{"key":"ref931","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.ymgme.2006.07.003","article-title":"Role of calcium-sensing receptor in mineral ion metabolism and inherited disorders of calcium-sensing","volume":"89","year":"2006","journal-title":"Molecular Genetics and Metabolism"},{"key":"ref431","doi-asserted-by":"crossref","first-page":"21708","DOI":"10.1074\/jbc.273.34.21708","article-title":"The calcium-sensing receptor is localized in caveolin-rich plasma membrane domains of bovine parathyroid cells","volume":"273","year":"1998","journal-title":"Journal of Biological Chemistry"},{"key":"ref1571","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1038\/nature13430","article-title":"Visualization of arrestin recruitment by a G-protein-coupled receptor","volume":"512","year":"2014","journal-title":"Nature"},{"key":"ref1381","doi-asserted-by":"crossref","first-page":"7254","DOI":"10.1074\/jbc.M307191200","article-title":"Homology modeling of the transmembrane domain of the human calcium sensing receptor and localization of an allosteric binding site","volume":"279","year":"2004","journal-title":"Journal of Biological Chemistry"},{"key":"ref1041","first-page":"32","article-title":"Cinacalcet rectifies hypercalcemia in a patient with familial hypocalciuric hypercalcemia type 2 (FHH2) caused by a germline loss-of-function Galpha11 mutation","volume":"33","year":"2017a","journal-title":"Journal of Bone and Mineral Research"},{"key":"ref131","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1038\/nchembio.206","article-title":"Sustained cyclic AMP production by parathyroid hormone receptor endocytosis","volume":"5","year":"2009","journal-title":"Nature Chemical Biology"},{"key":"ref1451","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1056\/NEJM199610103351505","article-title":"A familial syndrome of hypocalcemia with hypercalciuria due to mutations in the calcium-sensing receptor","volume":"335","year":"1996b","journal-title":"New England Journal of Medicine"},{"key":"ref261","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.beem.2013.04.007","article-title":"Calcium-sensing receptor (CaSR) mutations and disorders of calcium, electrolyte and water metabolism","volume":"27","year":"2013","journal-title":"Best Practice and Research: Clinical Endocrinology and Metabolism"},{"key":"ref291","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1126\/science.285.5431.1268","article-title":"AP-2 recruitment to synaptotagmin stimulated by tyrosine-based endocytic motifs","volume":"285","year":"1999","journal-title":"Science"},{"key":"ref361","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1016\/j.febslet.2006.02.035","article-title":"Silencing of filamin A gene expression inhibits Ca2+-sensing receptor signaling","volume":"580","year":"2006","journal-title":"FEBS Letters"},{"key":"ref241","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1210\/me.2012-1232","article-title":"Calcium signaling regulates trafficking of familial hypocalciuric hypercalcemia (FHH) mutants of the calcium sensing receptor","volume":"26","year":"2012","journal-title":"Molecular Endocrinology"},{"key":"ref761","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.ceca.2011.11.009","article-title":"Biased agonism of the calcium-sensing receptor","volume":"51","year":"2012","journal-title":"Cell Calcium"},{"key":"ref541","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1530\/JME-16-0184","article-title":"Filamin A is reduced and contributes to the CASR sensitivity in human parathyroid tumors","volume":"58","year":"2017","journal-title":"Journal of Molecular Endocrinology"},{"key":"ref1021","doi-asserted-by":"crossref","first-page":"e13662","DOI":"10.7554\/eLife.13662","article-title":"Structural mechanism of ligand activation in human calcium-sensing receptor","volume":"5","year":"2016","journal-title":"Elife"},{"key":"ref1661","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1016\/S0140-6736(02)09842-2","article-title":"Association between activating mutations of calcium-sensing receptor and Bartter\u2019s syndrome","volume":"360","year":"2002","journal-title":"Lancet"},{"key":"ref1601","doi-asserted-by":"crossref","first-page":"47438","DOI":"10.1074\/jbc.M408846200","article-title":"A novel Galphaq\/11-selective inhibitor","volume":"279","year":"2004","journal-title":"Journal of Biological Chemistry"},{"key":"ref211","doi-asserted-by":"crossref","first-page":"eaan3714","DOI":"10.1126\/scisignal.aan3714","article-title":"A calcium-sensing receptor mutation causing hypocalcemia disrupts a transmembrane salt bridge to activate \u03b2-arrestin biased signaling","volume":"11","year":"2018a","journal-title":"Sci Signal"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1038\/366575a0","article-title":"Cloning and characterization of an extracellular Ca(2+)-sensing receptor from bovine parathyroid","volume":"366","year":"1993","journal-title":"Nature"},{"key":"ref91","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/S0092-8674(02)00735-3","article-title":"Molecular architecture and functional model of the endocytic AP2 complex","volume":"109","year":"2002","journal-title":"Cell"},{"key":"ref191","first-page":"32","article-title":"Cinacalcet rectifies hypercalcemia in a patient with familial hypocalciuric hypercalcemia type 2 (FHH2) caused by a germline loss-of-function Galpha11 mutation","volume":"33","year":"2017a","journal-title":"Journal of Bone and Mineral Research"},{"key":"ref221","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1016\/j.celrep.2017.12.089","article-title":"AP2\u03c3 mutations impair calcium-sensing receptor trafficking and signaling revealing an endosomal pathway that spatially directs G-protein selectivity","volume":"22","year":"2018b","journal-title":"Cell Reports"},{"key":"ref1651","doi-asserted-by":"crossref","first-page":"14476","DOI":"10.1074\/jbc.273.23.14476","article-title":"Disulfide bonds in the extracellular calcium-polyvalent cation-sensing receptor correlate with dimer formation and its response to divalent cations in vitro","volume":"273","year":"1998","journal-title":"Journal of Biological Chemistry"},{"key":"ref271","doi-asserted-by":"crossref","first-page":"2768","DOI":"10.1093\/hmg\/dds105","article-title":"Identification of 70 calcium-sensing receptor mutations in hyper- and hypo-calcaemic patients: evidence for clustering of extracellular domain mutations at calcium-binding sites","volume":"21","year":"2012","journal-title":"Human Molecular Genetics"},{"key":"ref401","doi-asserted-by":"crossref","first-page":"3960","DOI":"10.1074\/jbc.M113.526350","article-title":"Spatially restricted G protein-coupled receptor activity via divergent endocytic compartments","volume":"289","year":"2014","journal-title":"Journal of Biological Chemistry"},{"key":"ref311","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1038\/nrm1154","article-title":"Extracellular calcium sensing and signalling","volume":"4","year":"2003","journal-title":"Nature Reviews Molecular Cell Biology"},{"key":"ref791","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1016\/j.jbspin.2009.02.001","article-title":"Familial hypocalciuric hypercalcemia revealed by chondrocalcinosis","volume":"76","year":"2009","journal-title":"Joint Bone Spine"},{"key":"ref1141","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1126\/science.285.5431.1268","article-title":"AP-2 recruitment to synaptotagmin stimulated by tyrosine-based endocytic motifs","volume":"285","year":"1999","journal-title":"Science"},{"key":"ref411","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/emm.2005.13","article-title":"Calcium sensing receptor forms complex with and is up-regulated by caveolin-1 in cultured human osteosarcoma (Saos-2) cells","volume":"37","year":"2005","journal-title":"Experimental and Molecular Medicine"},{"key":"ref1191","doi-asserted-by":"crossref","first-page":"5113","DOI":"10.1074\/jbc.M413403200","article-title":"A region in the seven-transmembrane domain of the human Ca2+ receptor critical for response to Ca2+","volume":"280","year":"2005","journal-title":"Journal of Biological Chemistry"},{"key":"ref1371","doi-asserted-by":"publisher","first-page":"2015","DOI":"10.1210\/jc.2014-4221","article-title":"Letter to the editor : distinguishing typical primary hyperparathyroidism from familial hypocalciuric hypercalcemia by using an index of urinary calcium of and https org","volume":"29","author":"MarxSJ","journal-title":"Journal Clinical Endocrinology Metabolism"},{"key":"ref1391","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1530\/JME-16-0184","article-title":"Filamin A is reduced and contributes to the CASR sensitivity in human parathyroid tumors","volume":"58","year":"2017","journal-title":"Journal of Molecular Endocrinology"},{"key":"ref1321","doi-asserted-by":"crossref","first-page":"4304","DOI":"10.1210\/en.2012-1449","article-title":"Identification of molecular phenotypes and biased signaling induced by naturally occurring mutations of the human calcium-sensing receptor","volume":"153","year":"2012","journal-title":"Endocrinology"},{"key":"ref1431","doi-asserted-by":"crossref","first-page":"2683","DOI":"10.1172\/JCI118335","article-title":"Calcium-sensing receptor mutations in familial benign hypercalcemia and neonatal hyperparathyroidism","volume":"96","year":"1995","journal-title":"Journal of Clinical Investigation"},{"key":"ref1121","doi-asserted-by":"crossref","first-page":"2768","DOI":"10.1093\/hmg\/dds105","article-title":"Identification of 70 calcium-sensing receptor mutations in hyper- and hypo-calcaemic patients: evidence for clustering of extracellular domain mutations at calcium-binding sites","volume":"21","year":"2012","journal-title":"Human Molecular Genetics"},{"key":"ref831","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1126\/science.1249489","article-title":"Structure of a class C GPCR metabotropic glutamate receptor 1 bound to an allosteric modulator","volume":"344","year":"2014","journal-title":"Science"},{"key":"ref1641","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1016\/j.jbspin.2009.02.001","article-title":"Familial hypocalciuric hypercalcemia revealed by chondrocalcinosis","volume":"76","year":"2009","journal-title":"Joint Bone Spine"},{"key":"ref781","doi-asserted-by":"crossref","first-page":"2259","DOI":"10.1097\/01.ASN.0000025781.16723.68","article-title":"Functional characterization of a calcium-sensing receptor mutation in severe autosomal dominant hypocalcemia with a Bartter-like syndrome","volume":"13","year":"2002","journal-title":"Journal of the American Society of Nephrology"},{"key":"ref961","doi-asserted-by":"crossref","first-page":"1916","DOI":"10.1210\/endo.138.5.5131","article-title":"N-linked glycosylation of the human Ca2+ receptor is essential for its expression at the cell surface","volume":"138","year":"1997","journal-title":"Endocrinology"},{"key":"ref621","doi-asserted-by":"crossref","first-page":"3830","DOI":"10.1210\/en.2002-220240","article-title":"Calcium-sensing receptor activation of Rho involves filamin and Rho-guanine nucleotide exchange factor","volume":"143","year":"2002","journal-title":"Endocrinology"},{"key":"ref881","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.beem.2013.03.003","article-title":"The calcium sensing receptor life cycle: trafficking, cell surface expression, and degradation","volume":"27","year":"2013","journal-title":"Best Practice and Research: Clinical Endocrinology and Metabolism"},{"key":"ref1511","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1016\/0092-8674(93)90617-Y","article-title":"Mutations in the human Ca(2+)-sensing receptor gene cause familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism","volume":"75","year":"1993","journal-title":"Cell"},{"key":"ref731","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1038\/nature09795","article-title":"The structural basis of agonist-induced activation in constitutively active rhodopsin","volume":"471","year":"2011","journal-title":"Nature"},{"key":"ref481","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1210\/en.2012-1887","article-title":"Impact of clinically relevant mutations on the pharmacoregulation and signaling bias of the calcium-sensing receptor by positive and negative allosteric modulators","volume":"154","year":"2013","journal-title":"Endocrinology"},{"key":"ref491","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1210\/jc.2014-1029","article-title":"Autosomal dominant hypoparathyroidism caused by germline mutation in phenotypic and molecular characterization of and https org","volume":"11","year":"2014","journal-title":"Journal Clinical Endocrinology Metabolism"},{"key":"ref1491","doi-asserted-by":"crossref","first-page":"2200","DOI":"10.1093\/hmg\/ddl145","article-title":"Calcium-sensing receptor dimerizes in the endoplasmic reticulum: biochemical and biophysical characterization of CASR mutants retained intracellularly","volume":"15","year":"2006","journal-title":"Human Molecular Genetics"},{"key":"ref1161","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1038\/nrm1154","article-title":"Extracellular calcium sensing and signalling","volume":"4","year":"2003","journal-title":"Nature Reviews Molecular Cell Biology"},{"key":"ref1271","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1038\/nature07422","article-title":"A structural explanation for the binding of endocytic dileucine motifs by the AP2 complex","volume":"456","year":"2008","journal-title":"Nature"},{"key":"ref711","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.tibs.2011.06.003","article-title":"Emerging paradigms of beta-arrestin-dependent seven transmembrane receptor signaling","volume":"36","year":"2011","journal-title":"Trends in Biochemical Sciences"},{"key":"ref1221","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/B978-0-12-385952-5.00007-5","article-title":"Regulation of stability and trafficking of calcium-sensing receptors by pharmacologic chaperones","volume":"62","year":"2011","journal-title":"Advances in Pharmacology"},{"key":"ref821","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1073\/pnas.1205756110","article-title":"Noncanonical GPCR signaling arising from a PTH receptor-arrestin-Gbetagamma complex","volume":"110","year":"2013","journal-title":"PNAS"},{"key":"ref1281","doi-asserted-by":"crossref","first-page":"21708","DOI":"10.1074\/jbc.273.34.21708","article-title":"The calcium-sensing receptor is localized in caveolin-rich plasma membrane domains of bovine parathyroid cells","volume":"273","year":"1998","journal-title":"Journal of Biological Chemistry"},{"key":"ref1541","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1152\/ajprenal.00608.2009","article-title":"RiccardiDBrownEM and pathophysiology of the calcium - sensing receptor in the kidney of https org","year":"2010","journal-title":"Physiology American Journal Physiology Renal Physiology"},{"key":"ref451","doi-asserted-by":"crossref","first-page":"a016725","DOI":"10.1101\/cshperspect.a016725","article-title":"Molecular structure, function, and dynamics of clathrin-mediated membrane traffic","volume":"6","year":"2014","journal-title":"Cold Spring Harbor Perspectives in Biology"},{"key":"ref1201","doi-asserted-by":"crossref","first-page":"21558","DOI":"10.1074\/jbc.M603682200","article-title":"A missense mutation in the seven-transmembrane domain of the human Ca2+ receptor converts a negative allosteric modulator into a positive allosteric modulator","volume":"281","year":"2006","journal-title":"Journal of Biological Chemistry"},{"key":"ref1561","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.tibs.2011.06.003","article-title":"Emerging paradigms of beta-arrestin-dependent seven transmembrane receptor signaling","volume":"36","year":"2011","journal-title":"Trends in Biochemical Sciences"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"e1000172","DOI":"10.1371\/journal.pbio.1000172","article-title":"Persistent cAMP-signals triggered by internalized G-protein-coupled receptors","volume":"7","year":"2009","journal-title":"PLoS Biology"},{"key":"ref771","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1002\/ajmg.a.30403","article-title":"A novel mutation (E767K) in the second extracellular loop of the calcium sensing receptor in a family with autosomal dominant hypocalcemia","volume":"132A","year":"2005","journal-title":"American Journal of Medical Genetics Part A"},{"key":"ref841","doi-asserted-by":"crossref","first-page":"e1600241","DOI":"10.1126\/sciadv.1600241","article-title":"Structural basis for regulation of human calcium-sensing receptor by magnesium ions and an unexpected tryptophan derivative co-agonist","volume":"2","year":"2016","journal-title":"Science Advances"},{"key":"ref421","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1038\/nature07422","article-title":"A structural explanation for the binding of endocytic dileucine motifs by the AP2 complex","volume":"456","year":"2008","journal-title":"Nature"},{"key":"ref471","doi-asserted-by":"crossref","first-page":"4304","DOI":"10.1210\/en.2012-1449","article-title":"Identification of molecular phenotypes and biased signaling induced by naturally occurring mutations of the human calcium-sensing receptor","volume":"153","year":"2012","journal-title":"Endocrinology"},{"key":"ref1291","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1152\/ajprenal.2001.280.2.F291","article-title":"Regulation of MAP kinase by calcium - sensing receptor in bovine parathyroid and CaR - transfected cells of https org","year":"2001","journal-title":"American Journal Physiology Renal Physiology"},{"key":"ref441","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1152\/ajprenal.2001.280.2.F291","article-title":"Regulation of MAP kinase by calcium - sensing receptor in bovine parathyroid and CaR - transfected cells of https org","year":"2001","journal-title":"American Journal Physiology Renal Physiology"},{"key":"ref1501","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1002\/jbmr.2797","article-title":"Identification of a G-protein subunit-alpha11 gain-of-function mutation, Val340Met, in a family with autosomal dominant hypocalcemia type 2 (ADH2)","volume":"31","year":"2016","journal-title":"Journal of Bone and Mineral Research"},{"key":"ref281","doi-asserted-by":"crossref","first-page":"5079","DOI":"10.1093\/hmg\/ddv226","article-title":"Adaptor protein-2 sigma subunit mutations causing familial hypocalciuric hypercalcaemia type 3 (FHH3) demonstrate genotype-phenotype correlations, codon bias and dominant-negative effects","volume":"24","year":"2015","journal-title":"Human Molecular Genetics"},{"key":"ref01","doi-asserted-by":"crossref","first-page":"29171","DOI":"10.1074\/jbc.M103747200","article-title":"Activation of the beta 2-adrenergic receptor involves disruption of an ionic lock between the cytoplasmic ends of transmembrane segments 3 and 6","volume":"276","year":"2001","journal-title":"Journal of Biological Chemistry"},{"key":"ref251","doi-asserted-by":"crossref","first-page":"e0136702","DOI":"10.1371\/journal.pone.0136702","article-title":"14-3-3 proteins buffer intracellular calcium sensing receptors to constrain signaling","volume":"10","year":"2015","journal-title":"PLoS ONE"},{"key":"ref981","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1038\/nchembio.206","article-title":"Sustained cyclic AMP production by parathyroid hormone receptor endocytosis","volume":"5","year":"2009","journal-title":"Nature Chemical Biology"},{"key":"ref811","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1016\/S0140-6736(02)09842-2","article-title":"Association between activating mutations of calcium-sensing receptor and Bartter\u2019s syndrome","volume":"360","year":"2002","journal-title":"Lancet"},{"key":"ref891","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1152\/physrev.1991.71.2.371","article-title":"Extracellular Ca2+ sensing, regulation of parathyroid cell function, and role of Ca2+ and other ions as extracellular (first) messengers","volume":"71","year":"1991","journal-title":"Physiological Reviews"},{"key":"ref1341","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1210\/jc.2014-1029","article-title":"Autosomal dominant hypoparathyroidism caused by germline mutation in phenotypic and molecular characterization of and https org","volume":"11","year":"2014","journal-title":"Journal Clinical Endocrinology Metabolism"},{"key":"ref1421","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1007\/s00431-008-0794-y","article-title":"Unusually severe phenotype of neonatal primary hyperparathyroidism due to a heterozygous inactivating mutation in the CASR gene","volume":"168","year":"2009","journal-title":"European Journal of Pediatrics"},{"key":"ref601","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1056\/NEJM199610103351505","article-title":"A familial syndrome of hypocalcemia with hypercalciuria due to mutations in the calcium-sensing receptor","volume":"335","year":"1996b","journal-title":"New England Journal of Medicine"},{"key":"ref1681","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1126\/science.1249489","article-title":"Structure of a class C GPCR metabotropic glutamate receptor 1 bound to an allosteric modulator","volume":"344","year":"2014","journal-title":"Science"},{"key":"ref151","doi-asserted-by":"crossref","first-page":"29712","DOI":"10.1074\/jbc.273.45.29712","article-title":"A carboxyl-terminal domain controls the cooperativity for extracellular Ca2+ activation of the human calcium sensing receptor. A study with receptor-green fluorescent protein fusions","volume":"273","year":"1998","journal-title":"Journal of Biological Chemistry"},{"key":"ref81","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.ymgme.2006.07.003","article-title":"Role of calcium-sensing receptor in mineral ion metabolism and inherited disorders of calcium-sensing","volume":"89","year":"2006","journal-title":"Molecular Genetics and Metabolism"},{"key":"ref1011","doi-asserted-by":"crossref","first-page":"39053","DOI":"10.1074\/jbc.M105662200","article-title":"Heterodimerization of calcium sensing receptors with metabotropic glutamate receptors in neurons","volume":"276","year":"2001","journal-title":"Journal of Biological Chemistry"},{"key":"ref591","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.1172\/JCI118987","article-title":"Functional characterization of calcium-sensing receptor mutations expressed in human embryonic kidney cells","volume":"98","year":"1996a","journal-title":"Journal of Clinical Investigation"},{"key":"ref1611","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.ceca.2011.11.009","article-title":"Biased agonism of the calcium-sensing receptor","volume":"51","year":"2012","journal-title":"Cell Calcium"},{"key":"ref521","doi-asserted-by":"publisher","first-page":"2015","DOI":"10.1210\/jc.2014-4221","article-title":"Letter to the editor : distinguishing typical primary hyperparathyroidism from familial hypocalciuric hypercalcemia by using an index of urinary calcium of and https org","volume":"29","author":"MarxSJ","journal-title":"Journal Clinical Endocrinology Metabolism"},{"key":"ref861","doi-asserted-by":"crossref","first-page":"4709","DOI":"10.1242\/jcs.02598","article-title":"Receptor-activity-modifying proteins are required for forward trafficking of the calcium-sensing receptor to the plasma membrane","volume":"118","year":"2005","journal-title":"Journal of Cell Science"},{"key":"ref1551","doi-asserted-by":"crossref","first-page":"10156","DOI":"10.1038\/ncomms10156","article-title":"The experimental power of FR900359 to study Gq-regulated biological processes","volume":"6","year":"2015","journal-title":"Nature Communications"},{"key":"ref1231","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1038\/nature12000","article-title":"Conformational biosensors reveal GPCR signalling from endosomes","volume":"495","year":"2013","journal-title":"Nature"},{"key":"ref1261","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/emm.2005.13","article-title":"Calcium sensing receptor forms complex with and is up-regulated by caveolin-1 in cultured human osteosarcoma (Saos-2) cells","volume":"37","year":"2005","journal-title":"Experimental and Molecular Medicine"},{"key":"ref921","doi-asserted-by":"crossref","first-page":"25030","DOI":"10.1074\/jbc.M700924200","article-title":"Complex formation with the Type B gamma-aminobutyric acid receptor affects the expression and signal transduction of the extracellular calcium-sensing receptor. Studies with HEK-293 cells and neurons","volume":"282","year":"2007","journal-title":"Journal of Biological Chemistry"},{"key":"ref511","doi-asserted-by":"crossref","first-page":"2532","DOI":"10.1056\/NEJMc1300278","article-title":"Germline mutations affecting Galpha11 in hypoparathyroidism","volume":"368","year":"2013","journal-title":"New England Journal of Medicine"},{"key":"ref971","doi-asserted-by":"crossref","first-page":"27849","DOI":"10.1074\/jbc.M112.445098","article-title":"Noncanonical control of vasopressin receptor type 2 signaling by retromer and arrestin","volume":"288","year":"2013","journal-title":"Journal of Biological Chemistry"},{"key":"ref801","doi-asserted-by":"crossref","first-page":"14476","DOI":"10.1074\/jbc.273.23.14476","article-title":"Disulfide bonds in the extracellular calcium-polyvalent cation-sensing receptor correlate with dimer formation and its response to divalent cations in vitro","volume":"273","year":"1998","journal-title":"Journal of Biological Chemistry"},{"key":"ref1081","first-page":"ra78","article-title":"Agonist-driven maturation and plasma membrane insertion of calcium-sensing receptors dynamically control signal amplitude","volume":"4","year":"2011","journal-title":"Science Signaling"}],"container-title":["Journal of Molecular Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/jme.bioscientifica.com\/view\/journals\/jme\/61\/1\/JME-18-0049.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1530\/JME-18-0049","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:53:31Z","timestamp":1784555611000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/jme\/article\/61\/1\/R1-R12\/14256"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7]]},"references-count":170,"journal-issue":{"issue":"1"},"URL":"https:\/\/doi.org\/10.1530\/jme-18-0049","relation":{},"ISSN":["0952-5041","1479-6813"],"issn-type":[{"value":"0952-5041","type":"print"},{"value":"1479-6813","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,7]]}}}