Identification of glycosylation sites essential for surface expression of the CaVα2δ1 subunit and modulation of the cardiac CaV1.2 channel activity

Journal of Biological Chemistry

Volumn 291, Issue 9, 2016, Pages 4826-4843

  Tétreault, Marie Philippe ^a   Bourdin, BenoÎte ^a   Briot, Julie ^a   Segura, Emilie ^a   Lesage, Sylvie ^c   Fiset, Céline ^b   Parent, Lucie ^a  

^a UNIVERSITÉ DE MONTRÉAL   (Canada)

^b MONTREAL HEART INSTITUTE   (Canada)

^c UNIVERSITY OF MONTREAL   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

CELL MEMBRANES; GLYCOSYLATION; HEART; PROTEINS; RECOMBINANT PROTEINS; STABILITY;

CARDIAC ARRHYTHMIA; CELL SURFACE DENSITY; ELECTRICAL REMODELING; GLYCOSYLATION SITES; PEAK CURRENT DENSITY; POST-TRANSLATIONAL MODIFICATIONS; REGULATORY SUBUNITS; SURFACE EXPRESSION;

CALCIUM;

ASPARAGINE; CALCIUM CHANNEL L TYPE; GLUTAMINE; UNCLASSIFIED DRUG; VOLTAGE GATED CALCIUM CHANNEL; VOLTAGE GATED CALCIUM CHANNEL 1 2; VOLTAGE GATED CALCIUM CHANNEL ALPHA2DELTA1 SUBUNIT; CACNA2D1 PROTEIN, RAT; HYBRID PROTEIN; L-TYPE CALCIUM CHANNEL ALPHA(1C); PHOTOPROTEIN; RECOMBINANT PROTEIN;

ADULT; ANIMAL CELL; ARTICLE; ASSAY; CALCIUM CURRENT; CELL DENSITY; CHANNEL GATING; CONFOCAL IMAGING; CONTROLLED STUDY; CURRENT DENSITY; CYCLOHEXIMIDE CHASE ASSAY; DEGRADATION KINETICS; DENSITY; EMBRYO; FLOW CYTOMETRY; FLUORESCENCE; HUMAN; HUMAN CELL; IMAGING; MALE; MOUSE; MUTATIONAL ANALYSIS; NEWBORN; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN DENSITY; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN GLYCOSYLATION; PROTEIN LOCALIZATION; PROTEIN STABILITY; PROTEIN SYNTHESIS; UPREGULATION; VOLTAGE DEPENDENT GATING; AMINO ACID SUBSTITUTION; ANIMAL; CARDIAC MUSCLE CELL; CELL CULTURE; CELL MEMBRANE; CHEMISTRY; CYTOLOGY; GENETICS; GLYCOSYLATION; HEK293 CELL LINE; METABOLISM; MOLECULAR WEIGHT; POINT MUTATION; PROTEIN PROCESSING; RABBIT; RAT; SITE DIRECTED MUTAGENESIS; SURFACE PROPERTY;

AMINO ACID SUBSTITUTION; ANIMALS; ANIMALS, NEWBORN; CALCIUM CHANNELS, L-TYPE; CELL MEMBRANE; CELLS, CULTURED; GLYCOSYLATION; HEK293 CELLS; HUMANS; LUMINESCENT PROTEINS; MOLECULAR WEIGHT; MUTAGENESIS, SITE-DIRECTED; MYOCYTES, CARDIAC; POINT MUTATION; PROTEIN PROCESSING, POST-TRANSLATIONAL; PROTEIN STABILITY; RABBITS; RATS; RECOMBINANT FUSION PROTEINS; RECOMBINANT PROTEINS; SURFACE PROPERTIES;

EID: 84964773925     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M115.692178     Document Type: Article

References (95)

1. Richard, S., Perrier, E., Fauconnier, J., Perrier, R., Pereira, L., Gomez, A. M. and Beńitah, J. P. (2006) Calcium-induced calcium entry or how the L-type calcium channel remodels its own signalling pathway in cardiac cells. Prog. Biophys. Mol. Biol. 90, 118-135.
2. Bers, D. M. (2000) Calcium fluxes involved in control of cardiac myocyte contraction. Circ. Res. 87, 275-281.
3. Kamp, T. J. and Hell, J. W. (2000) Regulation of cardiac L-type calcium channels by protein kinase A and protein kinase C. Circ. Res. 87, 1095-1102.
4. 2+channel surface expression and cerebrovascular constriction in genetic hypertension. Hypertension 60, 1006-1015.
5. Yue, L., Feng, J., Gaspo, R., Li, G. R., Wang, Z. and Nattel, S. (1997) Ionic remodeling underlying action potential changes in a canine model of atrial fibrillation. Circ. Res. 81, 512-525.
6. Van Wagoner, D. R., Pond, A. L., Lamorgese, M., Rossie, S. S., McCarthy, P. M. and Nerbonne, J. M. (1999) Atrial L-type calcium currents and human atrial fibrillation. Circ. Res. 85, 428-436.
7. Aschar-Sobbi, R., Izaddoustdar, F., Korogyi, A. S., Wang, Q., Farman, G. P., Yang, F., Yang, W., Dorian, D., Simpson, J. A., Tuomi, J. M., Jones, D. L., Nanthakumar, K., Cox, B., Wehrens, X. H., Dorian, P. and Backx, P. H. (2015) Increased atrial arrhythmia susceptibility induced by intense endurance exercise in mice requires TNFα. Nat. Commun. 6, 6018.
8. Lugenbiel, P., Wenz, F., Govorov, K., Schweizer, P. A., Katus, H. A. and Thomas, D. (2015) Atrial fibrillation complicated by heart failure induces distinct remodeling of calcium cycling proteins. PLoS ONE 10, e0116395.
9. Richard, S., Leclercq, F., Lemaire, S., Piot, C. and Nargeot, J. (1998) Calcium currents in compensated hypertrophy and heart failure. Cardiovasc. Res. 37, 300-311.
10. Mukherjee, R. and Spinale, F. G. (1998) L-type calcium channel abundance and function with cardiac hypertrophy and failure: A review. J. Mol. Cell. Cardiol. 30, 1899-1916.
11. 2+channels. Annu. Rev. Cell Dev. Biol. 16, 521-555.
12. 2+-dependent inactivation of L-type calcium channels. Neuron 22, 549-558.
13. Dolphin, A. C. (2009) Calcium channel diversity: multiple roles of calcium channel subunits. Curr. Opin. Neurobiol. 19, 237-244.
14. Dai, S., Hall, D. D. and Hell, J. W. (2009) Supramolecular assemblies and localized regulation of voltage-gated ion channels. Physiol. Rev. 89, 411-452.
15. Gao, T., Puri, T. S., Gerhardstein, B. L., Chien, A. J., Green, R. D. and Hosey, M. M. (1997) Identification and subcellular localization of the subunits of L-type calcium channels and adenylyl cyclase in cardiac myocytes. J. Biol. Chem. 272, 19401-19407.
16. Carl, S. L., Felix, K., Caswell, A. H., Brandt, N. R., Ball, W. J. Jr., Vaghy, P. L., Meissner, G. and Ferguson, D. G. (1995) Immunolocalization of sarcolemmal dihydropyridine receptor and sarcoplasmic reticular triadin and ryanodine receptor in rabbit ventricle and atrium. J. Cell Biol. 129, 673-682.
17. Bourdin, B., Marger, F., Wall-Lacelle, S., Schneider, T., Klein, H., Sauvé, R. and Parent, L. (2010) Molecular determinants of the Cavβ-induced plasma membrane targeting of the Cav1.2 channel. J. Biol. Chem. 285, 22853-22863.
18. Altier, C., Garcia-Caballero, A., Simms, B., You, H., Chen, L., Walcher, J., Tedford, H. W., Hermosilla, T. and Zamponi, G. W. (2011) The Cav[β] subunit prevents RFP2-mediated ubiquitination and proteasomal degradation of L-type channels. Nat. Neurosci. 14, 173-180.
19. Fuller-Bicer, G. A., Varadi, G., Koch, S. E., Ishii, M., Bodi, I., Kadeer, N., Muth, J. N., Mikala, G., Petrashevskaya, N. N., Jordan, M. A., Zhang, S. P., Qin, N., Flores, C. M., Isaacsohn, I., Varadi, M., et al. (2009) Targeted disruption of the voltage-dependent calcium channel α2/δ1 subunit. Am. J. Physiol. Heart Circ. Physiol 297, H117-H124.
20. Singer, D., Biel, M., Lotan, I., Flockerzi, V., Hofmann, F. and Dascal, N. (1991) The roles of the subunits in the function of the calcium channel. Science 253, 1553-1557.
21. 1E calcium channel. J. Membr. Biol. 160, 127-140.
22. Bourdin, B., Shakeri, B., Tétreault, M. P., Sauvé, R., Lesage, S. and Parent, L. (2015) Functional characterization of CaVa2d mutations associated with sudden cardiac death. J. Biol. Chem. 290, 2854-2869.
23. Yasuda, T., Chen, L., Barr, W., McRory, J. E., Lewis, R. J., Adams, D. J. and Zamponi, G. W. (2004) Auxiliary subunit regulation of high-voltage activated calcium channels expressed in mammalian cells. Eur. J. Neurosci. 20, 1-13.
24. Dolphin, A. C. (2013) The α2δ subunits of voltage-gated calcium channels. Biochim. Biophys. Acta 1828, 1541-1549.
25. Chang, F. C., and Hosey, M. M. (1988) Dihydropyridine and phenylalkylamine receptors associated with cardiac and skeletal muscle calcium channels are structurally different. J. Biol. Chem. 263, 18929-18937.
26. Marais, E., Klugbauer, N., and Hofmann, F. (2001) Calcium channel α2δ subunits: structure and gabapentin binding. Mol. Pharmacol. 59, 1243-1248.
27. 2-subunit and the ssociatedδpeptides. J. Biol. Chem. 266, 3287-3293.
28. 2+channel α2δ subunit: structural and functional features. Eur. J. Neurosci. 25, 1705-1710.
29. Davies, A., Kadurin, I., Alvarez-Laviada, A., Douglas, L., Nieto-Rostro, M., Bauer, C. S., Pratt, W. S., and Dolphin, A. C. (2010) The α2δ subunits of voltage-gated calcium channels form GPI-anchored proteins, a posttranslational modification essential for function. Proc. Natl. Acad. Sci. U.S.A. 107, 1654-1659.
30. Robinson, P., Etheridge, S., Song, L., Shah, R., Fitzgerald, E. M., and Jones, O. T. (2011) Targeting of voltage-gated calcium channel α2δ-1 subunit to lipid rafts is independent from a GPI-anchoring motif. PLoS ONE 6, e19802.
31. Gurnett, C. A., De Waard, M., and Campbell, K. P. (1996) Dual function of the voltage-dependent calcium channel α2δ subunit in current stimula-tion and subunit interaction. Neuron 16, 431-440.
32. Walsh, C. P., Davies, A., Butcher, A. J., Dolphin, A. C. and Kitmitto, A. (2009) Three-dimensional structure of CaV3.1. J. Biol. Chem. 284, 22310-22321.
33. Markkanen, P. M., and Petäjä-Repo, U. E. (2008) N-Glycan-mediated quality control in the endoplasmic reticulum is required for the expression of correctly foldedδ-opioid receptors at the cell surface. J. Biol. Chem. 283, 29086-29098.
34. Weng, T. Y., Chiu, W. T., Liu, H. S., Cheng, H. C., Shen, M. R., Mount, D. B. and Chou, C. Y. (2013) Glycosylation regulates the function and membrane localization of KCC4. Biochim. Biophys. Acta 1833, 1133-1146.
35. Lu, J., Robinson, J. M., Edwards, D. and Deutsch, C. (2001) T1-T1 interactions occur in ER membranes while nascent Kv peptides are still attached to ribosomes. Biochemistry 40, 10934-10946.
36. Vacher, H. and Trimmer, J. S. (2012) Trafficking mechanisms underlying neuronal voltage-gated ion channel localization at the axon initial segment. Epilepsia 53, 21-31.
37. Scott, H. and Panin, V. M. (2014) The role of protein N-glycosylation in neural transmission. Glycobiology 24, 407-417.
38. Aebi, M., Bernasconi, R., Clerc, S. and Molinari, M. (2010) N-Glycan structures: recognition and processing in the ER. Trends Biochem. Sci. 35, 74-82.
39. Ioffe, E. and Stanley, P. (1994) Mice lacking N-acetylglucosaminyltransferase I activity die at mid-gestation, revealing an essential role for complex or hybrid N-linked carbohydrates. Proc. Natl. Acad. Sci. U.S.A. 91, 728-732.
40. Dennis, J. W., Nabi, I. R. and Demetriou, M. (2009) Metabolism, cell surface organization, and disease. Cell 139, 1229-1241.
41. Park, K. H., Kwok, S. M., Sharon, C., Baerga, R., Berga, R. and Sesti, F. (2003) N-Glycosylation-dependent block is a novel mechanism for druginduced cardiac arrhythmia. FASEB J. 17, 2308-2309.
42. Schulze-Bahr, E., Wang, Q., Wedekind, H., Haverkamp, W., Chen, Q., Sun, Y., Rubie, C., Hordt, M., Towbin, J. A., Borggrefe, M., Assmann, G., Qu, X., Somberg, J. C., Breithardt, G., Oberti, C. and Funke, H. (1997) KCNE1 mutations cause jervell and Lange-Nielsen syndrome. Nat. Genet. 17, 267-268.
43. Bas, T., Gao, G. Y., Lvov, A., Chandrasekhar, K. D., Gilmore, R. and Kobertz, W. R. (2011) Post-translationalN-glycosylation of type I transmembrane KCNE1 peptides: implications for membrane protein biogenesis and disease. J. Biol. Chem. 286, 28150-28159.
44. Du, D., Yang, H., Norring, S. A. and Bennett, E. S. (2014) In-silico modeling of glycosylation modulation dynamics in hERG ion channels and cardiac electrical signals. IEEE J. Biomed. Health Inform. 18, 205-214.
45. Castellano, A., Wei, X., Birnbaumer, L. and Perez-Reyes, E. (1993) Cloning and expression of a third calcium channelβ subunit. J. Biol. Chem. 268, 3450-3455.
46. Shakeri, B., Bourdin, B., Demers-Giroux, P. O., Sauvé, R. and Parent, L. (2012) A quartet of leucine residues in the guanylate kinase domain of CaVβ determines the plasma membrane density of the CaV2.3 channel. J. Biol. Chem. 287, 32835-32847.
47. 2, andβ subunits of a novel human neuronal calcium channel subtype. Neuron 8, 71-84.
48. Grandy, S. A., Treṕanier-Boulay, V. and Fiset, C. (2007) Postnatal development has a marked effect on ventricular repolarization in mice. Am. J. Physiol. Heart Circ. Physiol 293, H2168-H2177.
49. Treṕanier-Boulay, V., Lupien, M. A., St-Michel, C. and Fiset, C. (2004) Postnatal development of atrial repolarization in the mouse. Cardiovasc. Res. 64, 84-93.
50. Lizotte, E., Tremblay, A., Allen, B. G. and Fiset, C. (2005) Isolation and characterization of subcellular protein fractions from mouse heart. Anal. Biochem. 345, 47-54.
51. Lee, G. H., Badorff, C. and Knowlton, K. U. (2000) Dissociation of sarcoglycans and the dystrophin carboxyl terminus from the sarcolemma in enteroviral cardiomyopathy. Circ. Res. 87, 489-495.
52. Clark, R. B., Tremblay, A., Melnyk, P., Allen, B. G., Giles, W. R., and Fiset, C. (2001) T-tubule localization of the inward-rectifier K(+) channel in mouse ventricular myocytes: A role in K+ accumulation. J. Physiol. 537, 979-992.
53. Wall-Lacelle, S., Hossain, M. I., Sauvé, R., Blunck, R. and Parent, L. (2011) Double mutant cycle analysis identified a critical leucine residue in IIS4-S5 linker for the activation of the Cav2.3 calcium channel. J. Biol. Chem. 286, 27197-27205.
54. Yifrach, O. and MacKinnon, R. (2002) Energetics of pore opening in a voltage-gated K+ channel. Cell 111, 231-239.
55. Stanley, P., Schachter, H. and Taniguchi, N. (2009) in Essentials of Glycobiology (Varki, A., Cummings, R. D., Esko, J. D., Freeze, H. H., Stanley, P., Bertozzi, C. R., Hart, G. W., and Etzler, M. E., eds) 2nd Ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York.
56. Kasturi, L., Chen, H. and Shakin-Eshleman, S. H. (1997) Regulation of N-linked core glycosylation: use of a site-directed mutagenesis approach to identify Asn-Xaa-Ser/Thr sequons that are poor oligosaccharide acceptors. Biochem. J. 323, 415-419.
57. Douglas, L., Davies, A., Wratten, J. and Dolphin, A. C. (2006) Do voltagegated calcium channelα2δsubunits require proteolytic processing intoα2 and δ to be functional? Biochem. Soc. Trans. 34, 894-898.
58. Davies, A., Douglas, L., Hendrich, J., Wratten, J., Tran Van Minh, A., Foucault, I., Koch, D., Pratt, W. S., Saibil, H. R. and Dolphin, A. C. (2006) The calcium channel α2δ2 subunit partitions with Cav2.1 into lipid rafts in cerebellum: implications for localization and function. J. Neurosci. 26, 8748-8757.
59. Blom, N., Sicheritz-Ponteń, T., Gupta, R., Gammeltoft, S. and Brunak, S. (2004) Prediction of post-translational glycosylation and phosphorylation of proteins from the amino acid sequence. Proteomics 4, 1633-1649.
60. Sandoval, A., Oviedo, N., Andrade, A. and Felix, R. (2004) Glycosylation of asparagines 136 and 184 is necessary for the α2δsubunit-mediated regulation of voltage-gated calcium channels. FEBS Lett. 576, 21-26.
61. Petrecca, K., Atanasiu, R., Akhavan, A. and Shrier, A. (1999) N-Linked glycosylation sites determine HERG channel surface membrane expression. J. Physiol. 515, 41-48.
62. Gong, Q., Anderson, C. L., January, C. T. and Zhou, Z. (2002) Role of glycosylation in cell surface expression and stability of HERG potassium channels. Am. J. Physiol. Heart Circ. Physiol. 283, H77-H84.
63. Cohen, S. A. and Levitt, L. K. (1993) Partial characterization of the rH1 sodium channel protein from rat heart using subtype-specific antibodies. Circ. Res. 73, 735-742.
64. Laedermann, C. J., Syam, N., Pertin, M., Decosterd, I. and Abriel, H. (2013) β1- And β3-voltage-gated sodium channel subunits modulate cell surface expression and glycosylation of Nav1.7 in HEK293 cells. Front. Cell. Neurosci. 7, 137.
65. Mercier, A., Cleḿent, R., Harnois, T., Bourmeyster, N., Bois, P. and Chatelier, A. (2015) Nav1.5 channels can reach the plasma membrane through distinct N-glycosylation states. Biochim. Biophys. Acta 1850, 1215-1223.
66. Wu, J., Yan, Z., Li, Z., Yan, C., Lu, S., Dong, M. and Yan, N. (2015) Structure of the voltage-gated calcium channel Cav1.1 complex. Science 350, 10.1126/science.aad2395.
67. Freeze, H. H. and Kranz, C. (2010) Endoglycosidase and glycoamidase release ofN-linked glycans. Curr. Protoc. Protein Sci. Chapter 12, Unit 12.4.
68. Glozman, R., Okiyoneda, T., Mulvihill, C. M., Rini, J. M., Barriere, H. and Lukacs, G. L. (2009) N-Glycans are direct determinants of CFTR folding and stability in secretory and endocytic membrane traffic. J. Cell Biol. 184, 847-862.
69. Muthusamy, S., Malhotra, P., Hosameddin, M., Dudeja, A. K., Borthakur, S., Saksena, S., Gill, R. K., Dudeja, P. K. and Alrefai, W. A. (2015) N-Glycosylation is essential for ileal ASBT function and protection against proteases. Am. J. Physiol. Cell Physiol. 308, C964-C971.
70. Rougier, J. S., Albesa, M., Syam, N., Halet, G., Abriel, H. and Viard, P. (2015) Ubiquitin-specific protease USP2-45 acts as a molecular switch to promoteα2δ1-induced downregulation of Cav1.2 channels. Pflugers Arch. 467, 1919-1929.
71. Suzuki, S., Shuto, T., Sato, T., Kaneko, M., Takada, T., Suico, M. A., Cyr, D. M., Suzuki, H. and Kai, H. (2014) Inhibition of post-translationalN-glycosylation by HRD1 that controls the fate of ABCG5/8 transporter. Sci. Rep. 4, 4258.
72. Comyn, S. A., Chan, G. T. and Mayor, T. (2014) False start: cotranslational protein ubiquitination and cytosolic protein quality control. J. Proteomics 100, 92-101.
73. Winchester, B. (2005) Lysosomal metabolism of glycoproteins. Glycobiology 15, 1R-15R.
74. Nakagawa, H., Wakabayashi-Nakao, K., Tamura, A., Toyoda, Y., Koshiba, S. and Ishikawa, T. (2009) Disruption of N-linked glycosylation enhances ubiquitin-mediated proteasomal degradation of the human ATP-binding cassette transporter ABCG2. FEBS J. 276, 7237-7252.
75. Hebert, D. N. and Molinari, M. (2012) Flagging and docking: dual roles for N-glycans in protein quality control and cellular proteostasis. Trends Biochem. Sci. 37, 404-410.
76. Cassidy, J. S., Ferron, L., Kadurin, I., Pratt, W. S. and Dolphin, A. C. (2014) Functional exofacially tagged N-type calcium channels elucidate the interaction with auxiliary α2δ1 subunits. Proc. Natl. Acad. Sci. U.S.A. 111, 8979-8984.
77. 2+channels. Proc. Natl. Acad. Sci. U.S.A. 102, 11230-11235.
78. Gee, N. S., Brown, J. P., Dissanayake, V. U., Offord, J., Thurlow, R. and Woodruff, G. N. (1996) The novel anticonvulsant drug, gabapentin (Neurontin), binds to the α2δ subunit of a calcium channel. J. Biol. Chem. 271, 5768-5776.
79. (2008) Pharmacological disruption of calcium channel trafficking by the α2δ ligand gabapentin. Proc. Natl. Acad. Sci. U.S.A. 105, 3628-3633.
80. Song, L., Espinoza-Fuenzalida, I. A., Etheridge, S., Jones, O. T. and Fitzgerald, E. M. (2015) The R-domain: identification of an N-terminal region of the α2δ-1 subunit which is necessary and sufficient for its effects on Cav2.2 calcium currents. Curr. Mol. Pharmacol. 8, 169-179.
81. Ruscic, K. J., Miceli, F., Villalba-Galea, C. A., Dai, H., Mishina, Y., Bezanilla, F. and Goldstein, S. A. (2013) IKs channels open slowly because KCNE1 accessory subunits slow the movement of S4 voltage sensors in KCNQ1 pore-forming subunits. Proc. Natl. Acad. Sci. U.S.A. 110, E559-E566.
82. Berrou, L., Klein, H., Bernatchez, G. and Parent, L. (2002) A specific tryptophan in the I-II linker is a key determinant of β-subunit binding and modulation in CaV2.3 calcium channels. Biophys. J 83, 1429-1442.
83. Berrou, L., Dodier, Y., Raybaud, A., Tousignant, A., Dafi, O., Pelletier, J. N. and Parent, L. (2005) The C-terminal residues in theα -interacting domain (AID) helix anchor CaV β subunit interaction and modulation of CaV2.3 channels. J. Biol. Chem. 280, 494-505.
84. Buraei, Z. and Yang, J. (2013) Structure and function of theβ subunit of voltage-gated calcium channels. Biochim. Biophys. Acta. 1828, 1530-1540.
85. Plant, L. D., Xiong, D., Dai, H. and Goldstein, S. A. (2014) Individual IKs channels at the surface of mammalian cells contain two KCNE1 accessory subunits. Proc. Natl. Acad. Sci. U.S.A. 111, E1438-E1446.
86. Burashnikov, E., Pfeiffer, R., Barajas-Martinez, H., Delpón, E., Hu, D., Desai, M., Borggrefe, M., Haïssaguerre, M., Kanter, R., Pollevick, G. D., Guerchicoff, A., Lainõ, R., Marieb, M., Nademanee, K., Nam, G. B., et al. (2010) Mutations in the cardiac L-type calcium channel associated with inherited J-wave syndromes and sudden cardiac death. Heart Rhythm. 7, 1872-1882.
87. Antzelevitch, C., Pollevick, G. D., Cordeiro, J. M., Casis, O., Sanguinetti, M. C., Aizawa, Y., Guerchicoff, A., Pfeiffer, R., Oliva, A., Wollnik, B., Gelber, P., Bonaros, E. P. Jr., Burashnikov, E., Wu, Y., Sargent, J. D., et al. (2007) Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death. Circulation 115, 442-449.
88. Templin, C., Ghadri, J. R., Rougier, J. S., Baumer, A., Kaplan, V., Albesa, M., Sticht, H., Rauch, A., Puleo, C., Hu, D., Barajas-Martinez, H., Antzelevitch, C., Luscher, T. F., Abriel, H. and Duru, F. (2011) Identification of a novel loss-of-function calcium channel gene mutation in short QT syndrome (SQTS6). Eur. Heart J. 32, 1077-1088.
89. Wormald, M. R. and Dwek, R. A. (1999) Glycoproteins: glycan presentation and protein-fold stability. Structure 7, R155-R160.
90. Zhao, Y., Sato, Y., Isaji, T., Fukuda, T., Matsumoto, A., Miyoshi, E., Gu, J. and Taniguchi, N. (2008) BranchedN-glycans regulate the biological functions of integrins and cadherins. FEBS J. 275, 1939-1948.
91. Nagae, M. and Yamaguchi, Y. (2012) Function and 3D structure of the N-glycans on glycoproteins. Int. J. Mol. Sci. 13, 8398-8429.
92. Pertusa, M., Madrid, R., Morenilla-Palao, C., Belmonte, C. and Viana, F. (2012) N-Glycosylation of TRPM8 ion channels modulates temperature sensitivity of cold thermoreceptor neurons. J. Biol. Chem. 287, 18218-18229.
93. Watanabe, I., Wang, H. G., Sutachan, J. J., Zhu, J., Recio-Pinto, E. and Thornhill, W. B. (2003) Glycosylation affects rat Kv1.1 potassium channel gating by a combined surface potential and cooperative subunit interaction mechanism. J. Physiol. 550, 51-66.
94. Ohtsubo, K. and Marth, J. D. (2006) Glycosylation in cellular mechanisms of health and disease. Cell 126, 855-867.
95. Brundel, B. J., van Gelder, I. C., Henning, R. H., Tuinenburg, A. E., Deelman, L. E., Tieleman, R. G., Grandjean, J. G., van Gilst, W. H. and Crijns, H. J. (1999) Gene expression of proteins influencing the calcium homeostasis in patients with persistent and paroxysmal atrial fibrillation. Cardiovasc. Res. 42, 443-454.