A G-protein Subunit-α11 Loss-of-Function Mutation, Thr54Met, Causes Familial Hypocalciuric Hypercalcemia Type 2 (FHH2)

Journal of Bone and Mineral Research

Volumn 31, Issue 6, 2016, Pages 1200-1206

  Gorvin, Caroline M ^a   Cranston, Treena ^b   Hannan, Fadil M ^a,c   Rust, Nigel ^d   Qureshi, Asjid ^e   Nesbit, M Andrew ^a,f   Thakker, Rajesh V ^a  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b CHURCHILL HOSPITAL   (United Kingdom)

^c UNIVERSITY OF LIVERPOOL   (United Kingdom)

^d UNIVERSITY OF OXFORD   (United Kingdom)

^e EALING HOSPITAL NHS TRUST   (United Kingdom)

^f UNIVERSITY OF ULSTER   (United Kingdom)

Author keywords

CELL TISSUE SIGNALING ENDOCRINE PATHWAYS; DISORDERS OF CALCIUM PHOSPHATE METABOLISM; PARATHYROID RELATED DISORDERS; PTH VIT D FGF23

Indexed keywords

CALCIUM; CALNEXIN; G PROTEIN SUBUNIT ALPHA 11; METHIONINE; PROTEIN; THREONINE; UNCLASSIFIED DRUG; CALCIUM SENSING RECEPTOR; CASR PROTEIN, HUMAN; GNA11 PROTEIN, HUMAN; GUANINE NUCLEOTIDE BINDING PROTEIN ALPHA SUBUNIT;

AGED; ARTICLE; CALCIUM CELL LEVEL; CASE REPORT; DNA SEQUENCE; EC50; EXTRACELLULAR CALCIUM; FAMILIAL DISEASE; FAMILIAL HYPOCALCIURIC HYPERCALCEMIA TYPE 2; FEMALE; FLOW CYTOMETRY; FLUORESCENCE MICROSCOPY; GENETIC CONSERVATION; HEK293 CELL LINE; HUMAN; HYPERCALCEMIA; HYPOCALCIURIA; LOSS OF FUNCTION MUTATION; MUTATIONAL ANALYSIS; PROTEIN FUNCTION; PROTEIN STRUCTURE; SIGNAL TRANSDUCTION; WESTERN BLOTTING; AMINO ACID SUBSTITUTION; CALCIUM SIGNALING; CHEMISTRY; GENETICS; METABOLISM; MISSENSE MUTATION; PATHOLOGY; PROTEIN DOMAIN;

AGED; AMINO ACID SUBSTITUTION; CALCIUM SIGNALING; FEMALE; GTP-BINDING PROTEIN ALPHA SUBUNITS; HEK293 CELLS; HUMANS; HYPERCALCEMIA; MUTATION, MISSENSE; PROTEIN DOMAINS; RECEPTORS, CALCIUM-SENSING;

EID: 84959228183     PISSN: 08840431     EISSN: 15234681     Source Type: Journal    
DOI: 10.1002/jbmr.2778     Document Type: Article

References (36)

1. Hannan FM, Thakker RV., Calcium-sensing receptor (CaSR) mutations and disorders of calcium, electrolyte and water metabolism. Best Pract Res Clin Endocrinol Metab. 2013; 27 (3): 359-71.
2. Eastell R, Brandi ML, Costa AG, D'Amour P, Shoback DM, Thakker RV., Diagnosis of asymptomatic primary hyperparathyroidism: proceedings of the Fourth International Workshop. J Clin Endocrinol Metab. 2014; 99 (10): 3570-9.
3. Hannan FM, Nesbit MA, Zhang C, 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. 2012; 21 (12): 2768-78.
4. Wu DQ, Lee CH, Rhee SG, Simon MI., Activation of phospholipase C by the alpha subunits of the Gq and G11 proteins in transfected Cos-7 cells. J Biol Chem. 1992; 267 (3): 1811-7.
5. Hofer AM, Brown EM., Extracellular calcium sensing and signalling. Nat Rev Mol Cell Biol. 2003; 4 (7): 530-8.
6. Breitwieser GE, Gama L., Calcium-sensing receptor activation induces intracellular calcium oscillations. Am J Physiol Cell Physiol. 2001; 280 (6): C1412-21.
7. Kumar R, Thompson JR., The regulation of parathyroid hormone secretion and synthesis. J Am Soc Nephrol. 2011; 22 (2): 216-24.
8. Quinn SJ, Kifor O, Kifor I, Butters RR Jr, Brown EM., Role of the cytoskeleton in extracellular calcium-regulated PTH release. Biochem Biophys Res Commun. 2007; 354 (1): 8-13.
9. Gong Y, Hou J., Claudin-14 underlies Ca(+)(+)-sensing receptor-mediated Ca(+)(+) metabolism via NFAT-microRNA-based mechanisms. J Am Soc Nephrol. 2014; 25 (4): 745-60.
10. Riccardi D, Brown EM., Physiology and pathophysiology of the calcium-sensing receptor in the kidney. Am J Physiol Renal Physiol. 2010; 298 (3): F485-99.
11. Nesbit MA, Hannan FM, Howles SA, et al., Mutations affecting G-protein subunit alpha11 in hypercalcemia and hypocalcemia. N Engl J Med. 2013; 368 (26): 2476-86.
12. Nesbit MA, Hannan FM, Howles SA, et al., Mutations in AP2S1 cause familial hypocalciuric hypercalcemia type 3. Nat Genet. 2013; 45 (1): 93-7.
13. Hannan FM, Howles SA, Rogers A, et al., Adaptor protein-2 sigma subunit mutations causing familial hypocalciuric hypercalcaemia type 3 (FHH3) demonstrate genotype-phenotype correlations, codon bias and dominant-negative effects. Hum Mol Genet. 2015; 24 (18): 5079-92.
14. Tenhola S, Hendy GN, Valta H, et al., Cinacalcet treatment in an adolescent with concurrent 22q11.2 deletion syndrome and familial hypocalciuric hypercalcemia type 3 caused by AP2S1 mutation. J Clin Endocrinol Metab. 2015; 100 (7): 2515-8.
15. Fujisawa Y, Yamaguchi R, Satake E, et al., Identification of AP2S1 mutation and effects of low calcium formula in an infant with hypercalcemia and hypercalciuria. J Clin Endocrinol Metab. 2013; 98 (12): E2022-7.
16. Hendy GN, Canaff L, Newfield RS, et al., Codon Arg15 mutations of the AP2S1 gene: common occurrence in familial hypocalciuric hypercalcemia cases negative for calcium-sensing receptor (CASR) mutations. J Clin Endocrinol Metab. 2014; 99 (7): E1311-5.
17. Sievers F, Wilm A, Dineen D, et al., Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol Syst Biol. 2011; 7: 539.
18. Nishimura A, Kitano K, Takasaki J, et al., Structural basis for the specific inhibition of heterotrimeric Gq protein by a small molecule. Proc Natl Acad Sci USA. 2010; 107 (31): 13666-71.
19. Newey PJ, Gorvin CM, Cleland SJ, et al., Mutant prolactin receptor and familial hyperprolactinemia. N Engl J Med. 2013; 369 (21): 2012-20.
20. Kumar P, Henikoff S, Ng PC,. Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc. 2009; 4 (7): 1073-81.
21. Schwarz JM, Cooper DN, Schuelke M, Seelow D., MutationTaster2: mutation prediction for the deep-sequencing age. Nat Methods. 2014; 11 (4): 361-2.
22. Sun D, Flock T, Deupi X, et al., Probing Galphai1 protein activation at single-amino acid resolution. Nat Struct Mol Biol. 2015; 22 (9): 686-94.
23. Bourne HR, Sanders DA, McCormick F., The GTPase superfamily: conserved structure and molecular mechanism. Nature. 1991; 349 (6305): 117-27.
24. Wittinghofer A, Vetter IR., Structure-function relationships of the G domain, a canonical switch motif. Annu Rev Biochem. 2011; 80: 943-71.
25. Barbacid M., Ras genes. Annu Rev Biochem. 1987; 56: 779-827.
26. Flock T, Ravarani CN, Sun D, et al., Universal allosteric mechanism for Galpha activation by GPCRs. Nature. 2015; 524 (7564): 173-9.
27. Pearce SH, Bai M, Quinn SJ, Kifor O, Brown EM, Thakker RV., Functional characterization of calcium-sensing receptor mutations expressed in human embryonic kidney cells. J Clin Invest. 1996; 98 (8): 1860-6.
28. Pi M, Chen L, Huang M, Luo Q, Quarles LD., Parathyroid-specific interaction of the calcium-sensing receptor and G alpha q. Kidney Int. 2008; 74 (12): 1548-56.
29. Wettschureck N, Lee E, Libutti SK, Offermanns S, Robey PG, Spiegel AM., Parathyroid-specific double knockout of Gq and G11 alpha-subunits leads to a phenotype resembling germline knockout of the extracellular Ca2+-sensing receptor. Mol Endocrinol. 2007; 21 (1): 274-80.
30. Oldham WM, Hamm HE., Heterotrimeric G protein activation by G-protein-coupled receptors. Nat Rev Mol Cell Biol. 2008; 9 (1): 60-71.
31. Li D, Opas EE, Tuluc F, et al., Autosomal dominant hypoparathyroidism caused by germline mutation in GNA11: phenotypic and molecular characterization. J Clin Endocrinol Metab. 2014; 99 (9): E1774-83.
32. Mannstadt M, Harris M, Bravenboer B, et al., Germline mutations affecting Galpha11 in hypoparathyroidism. N Engl J Med. 2013; 368 (26): 2532-4.
33. Bosch DE, Willard FS, Ramanujam R, et al., A P-loop mutation in Galpha subunits prevents transition to the active state: implications for G-protein signaling in fungal pathogenesis. PLoS Pathog. 2012; 8 (2): e1002553.
34. Yu B, Gu L, Simon MI., Inhibition of subsets of G protein-coupled receptors by empty mutants of G protein alpha subunits in g(o), G(11), and G(16). J Biol Chem. 2000; 275 (1): 71-6.
35. Shim JY, Ahn KH, Kendall DA., Molecular basis of cannabinoid CB1 receptor coupling to the G protein heterotrimer Galphaibetagamma: identification of key CB1 contacts with the C-terminal helix alpha5 of Galphai. J Biol Chem. 2013; 288 (45): 32449-65.
36. Liu W, Northup JK., The helical domain of a G protein alpha subunit is a regulator of its effector. Proc Natl Acad Sci USA. 1998; 95 (22): 12878-83.