Kniazeff, J., Prézeau, L., Rondard, P., Pin, J.-P. & Goudet, C. Dimers and beyond: the functional puzzles of class C GPCRs. Pharmacol. Ther. 130, 9–25 (2011).
Hofer, A. M. & Brown, E. M. Extracellular calcium sensing and signalling. Nat. Rev. Mol. Cell Biol. 4, 530–538 (2003).
Hannan, F. M., Kallay, E., Chang, W., Brandi, M. L. & Thakker, R. V. The calcium-sensing receptor in physiology and in calcitropic and noncalcitropic diseases. Nat. Rev. Endocrinol. 15, 33–51 (2019).
Vahe, C. et al. Diseases associated with calcium-sensing receptor. Orphanet J. Rare Dis. 12, 19 (2017).
Massy, Z. A., Henaut, L., Larsson, T. E. & Vervloet, M. G. Calcium-sensing receptor activation in chronic kidney disease: effects beyond parathyroid hormone control. Semin. Nephrol. 34, 648–659 (2014).
Eckardt, K.-U. et al. Evolving importance of kidney disease: from subspecialty to global health burden. Lancet 382, 158–169 (2013).
Niswender, C. M. & Conn, P. J. Metabotropic glutamate receptors: physiology, pharmacology, and disease. Annu. Rev. Pharmacol. Toxicol. 50, 295–322 (2010).
Gregory, K. J. & Goudet, C. International union of basic and clinical pharmacology. CXI. Pharmacology, signaling, and physiology of metabotropic glutamate receptors. Pharmacol. Rev. 73, 521–569 (2021).
Leach, K. et al. International Union of Basic and Clinical Pharmacology. CVIII. Calcium-sensing receptor nomenclature, pharmacology, and function. Pharmacol. Rev. 72, 558–604 (2020).
Seven, A. B. et al. G-protein activation by a metabotropic glutamate receptor. Nature 595, 450–454 (2021).
Lin, S. et al. Structures of Gi-bound metabotropic glutamate receptors mGlu2 and mGlu4. Nature 594, 583–588 (2021).
Shen, C. et al. Structural basis of GABAB receptor–Gi protein coupling. Nature 594, 594–598 (2021).
Magno, A. L., Ward, B. K. & Ratajczak, T. The calcium-sensing receptor: a molecular perspective. Endocr. Rev. 32, 3–30 (2011).
Centeno, P. P. et al. Phosphate acts directly on the calcium-sensing receptor to stimulate parathyroid hormone secretion. Nat. Commun. 10, 4693 (2019).
Leach, K. et al. Towards a structural understanding of allosteric drugs at the human calcium-sensing receptor. Cell Res. 26, 574–592 (2016).
Ling, S. et al. Structural mechanism of cooperative activation of the human calcium-sensing receptor by Ca2+ ions and l-tryptophan. Cell Res. 31, 383–394 (2021).
Gao, Y. et al. Asymmetric activation of the calcium-sensing receptor homodimer. Nature 595, 455–459 (2021).
Park, J. et al. Symmetric activation and modulation of the human calcium-sensing receptor. Proc. Natl Acad. Sci. USA 118, e2115849118 (2021).
Olsen, R. H. et al. TRUPATH, an open-source biosensor platform for interrogating the GPCR transducerome. Nat. Chem. Biol. 16, 841–849 (2020).
Masuho, I. et al. Distinct profiles of functional discrimination among G proteins determine the actions of G protein–coupled receptors. Sci. Signal. 8, ra123 (2015).
Wall, M. A. et al. The structure of the G-protein heterotrimer Giα1β1γ2. Cell 83, 1047–1058 (1995).
Duan, J. et al. Cryo-EM structure of an activated VIP1 receptor-G protein complex revealed by a NanoBiT tethering strategy. Nat. Commun. 11, 4121 (2020).
Timmers, H., Karperien, M., Hamdy, N., De Boer, H. & Hermus, A. Normalization of serum calcium by cinacalcet in a patient with hypercalcaemia due to a de novo inactivating mutation of the calcium-sensing receptor. J. Intern. Med. 260, 177–182 (2006).
Hannan, F. M. et al. Identification of 70 calcium-sensing receptor mutations in hyper-and hypo-calcaemic patients: evidence for clustering of extracellular domain mutations at calcium-binding sites. Hum. Mol. Genet. 21, 2768–2778 (2012).
Nagase, T. et al. A family of autosomal dominant hypocalcemia with a positive correlation between serum calcium and magnesium: identification of a novel gain of function mutation (Ser820Phe) in the calcium-sensing receptor. J. Clin. Endocrinol. Metab. 87, 2681–2687 (2002).
Shiohara, M. et al. A novel gain-of-function mutation (F821L) in the transmembrane domain of calcium-sensing receptor is a cause of severe sporadic hypoparathyroidism. Eur. J. Pediatr. 163, 94–98 (2004).
Hu, J. et al. A region in the seven-transmembrane domain of the human Ca2+ receptor critical for response to Ca2+. J. Biol. Chem. 280, 5113–5120 (2005).
Quinn, S. J. et al. The Ca2+-sensing receptor: a target for polyamines. Am. J. Physiol. 273, C1315–C1323 (1997).
Michael, A. J. Polyamines in eukaryotes, bacteria, and archaea. J. Biol. Chem. 291, 14896–14903 (2016).
Schamber, M. R. & Vafabakhsh, R. Mechanism of sensitivity modulation in the calcium-sensing receptor via electrostatic tuning. Nat. Commun. 13, 2194 (2022).
Cole, D. E. et al. Calcium-sensing receptor mutations and denaturing high performance liquid chromatography. J. Mol. Endocrinol. 42, 331–339 (2009).
Tan, Y. et al. Autosomal dominant hypocalcemia: a novel activating mutation (E604K) in the cysteine-rich domain of the calcium-sensing receptor. J. Clin. Endocrinol. Metab. 88, 605–610 (2003).
Kwan, B. et al. A novel CASR mutation (p. Glu757Lys) causing autosomal dominant hypocalcaemia type 1. Endocrinol. Diabetes Metab. Case Rep. 2018, 18-0107 (2018).
Conigrave, A. D., Quinn, S. J. & Brown, E. M. l-amino acid sensing by the extracellular Ca2+-sensing receptor. Proc. Natl Acad. Sci. USA 97, 4814–4819 (2000).
Mangmool, S. & Kurose, H. Gi/o protein-dependent and-independent actions of pertussis toxin (PTX). Toxins 3, 884–899 (2011).
Vargas-Poussou, R. et al. Familial hypocalciuric hypercalcemia types 1 and 3 and primary hyperparathyroidism: similarities and differences. J. Clin. Endocrinol. Metab. 101, 2185–2195 (2016).
Koltin, D. et al. Mild infantile hypercalcemia: diagnostic tests and outcomes. J. Pediatr. 159, 215–221 (2011).
Ray, K., Fan, G.-F., Goldsmith, P. K. & Spiegel, A. M. The carboxyl terminus of the human calcium receptor: requirements for cell-surface expression and signal transduction. J. Biol. Chem. 272, 31355–31361 (1997).
Nesbit, M. A. et al. Mutations affecting G-protein subunit α11 in hypercalcemia and hypocalcemia. N. Engl. J. Med. 368, 2476–2486 (2013).
Bai, M. et al. Protein kinase C phosphorylation of threonine at position 888 in Ca2+o-sensing receptor (CaR) inhibits coupling to Ca2+ store release. J. Biol. Chem. 273, 21267–21275 (1998).
Davies, S. L., Ozawa, A., McCormick, W. D., Dvorak, M. M. & Ward, D. T. Protein kinase C-mediated phosphorylation of the calcium-sensing receptor is stimulated by receptor activation and attenuated by calyculin-sensitive phosphatase activity. J. Biol. Chem. 282, 15048–15056 (2007).
Jiang, Y. F. et al. Protein kinase C (PKC) phosphorylation of the Ca2+o-sensing receptor (CaR) modulates functional interaction of G proteins with the CaR cytoplasmic tail. J. Biol. Chem. 277, 50543–50549 (2002).
Lazarus, S. et al. A novel mutation of the primary protein kinase C phosphorylation site in the calcium-sensing receptor causes autosomal dominant hypocalcemia. Eur. J. Endocrinol. 164, 429–435 (2011).
Brown, E. M. et al. Cloning and characterization of an extracellular Ca2+-sensing receptor from bovine parathyroid. Nature 366, 575–580 (1993).
Robertson, M. J., Meyerowitz, J. G., Panova, O., Borrelli, K. & Skiniotis, G. Plasticity in ligand recognition at somatostatin receptors. Nat. Struct. Mol. Biol. 29, 210–217 (2022).
Maeda, S. et al. Development of an antibody fragment that stabilizes GPCR/G-protein complexes. Nat. Commun. 9, 3712 (2018).
Bayburt, T. H., Grinkova, Y. V. & Sligar, S. G. Self-assembly of discoidal phospholipid bilayer nanoparticles with membrane scaffold proteins. Nano Lett. 2, 853–856 (2002).
Peisley, A. & Skiniotis, G. 2D projection analysis of GPCR complexes by negative stain electron microscopy. Methods Mol. Biol. 1335, 29–38 (2015).
Mastronarde, D. N. Automated electron microscope tomography using robust prediction of specimen movements. J. Struct. Biol. 152, 36–51 (2005).
Punjani, A., Rubinstein, J. L., Fleet, D. J. & Brubaker, M. A. cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nat. Methods 14, 290–296 (2017).
Zivanov, J. et al. New tools for automated high-resolution cryo-EM structure determination in RELION-3. eLife 7, e42166 (2018).
Pettersen, E. F. et al. UCSF Chimera—a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605–1612 (2004).
Zhang, X. et al. Structures of the human cholecystokinin receptors bound to agonists and antagonists. Nat. Chem. Biol. 17, 1230–1237 (2021).
Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D 66, 486–501 (2010).
Liebschner, D. et al. Macromolecular structure determination using X-rays, neutrons and electrons: recent developments in Phenix. Acta Crystallogr. D 75, 861–877 (2019).
Chen, V. B. et al. MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr. D 66, 12–21 (2010).
Pettersen, E. F. et al. UCSF ChimeraX: structure visualization for researchers, educators, and developers. Protein Sci. 30, 70–82 (2021).
Falk‐Petersen, C. B. et al. Development of a robust mammalian cell‐based assay for studying recombinant α4β1/3δ GABAA receptor subtypes. Basic Clin. Pharmacol. Toxicol. 121, 119–129 (2017).