A single amino acid deletion (ΔF1502) in the S6 segment of CaV2.1 domain III associated with congenital ataxia increases channel activity and promotes Ca2+ influx

PLoS ONE

Volumn 10, Issue 12, 2015, Pages

  Bahamonde, Maria Isabel ^a   Serra, Selma Angèlica ^a   Drechsel, Oliver ^a,b   Rahman, Rubayte ^a,b   Marcé Grau, Anna ^c   Prieto, Marta ^a   Ossowski, Stephan ^a,b   Macaya, Alfons ^c   Fernández Fernández, José M ^a  

^a UNIVERSITAT POMPEU FABRA   (Spain)

^b BARCELONA INSTITUTE OF SCIENCE AND TECHNOLOGY   (Spain)

^c UNIVERSITAT AUTÒNOMA DE BARCELONA   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

CALCIUM CHANNEL CAV2.1; PHENYLALANINE; UNCLASSIFIED DRUG; VOLTAGE GATED CALCIUM CHANNEL; CALCIUM; CALCIUM CHANNEL N TYPE; VOLTAGE-DEPENDENT CALCIUM CHANNEL (P-Q TYPE);

AMINO ACID DELETION; ARTICLE; ATAXIA; CACNA1A GENE; CALCIUM TRANSPORT; CASE REPORT; CELL MEMBRANE DEPOLARIZATION; CHILD; CONGENITAL ATAXIA; CONTROLLED STUDY; DISEASE ASSOCIATION; EMBRYO; EXOME; GAIN OF FUNCTION MUTATION; GENE DELETION; GENE FUNCTION; GENE SEQUENCE; HEK201 CELL LINE; HUMAN; HUMAN CELL; HYPERPOLARIZATION; MALE; NUCLEAR MAGNETIC RESONANCE IMAGING; PRESCHOOL CHILD; PROTEIN DOMAIN; PROTEIN MODIFICATION; SCHOOL CHILD; SITE DIRECTED MUTAGENESIS; BRAIN; GENETICS; METABOLISM; NEUROIMAGING; PATHOLOGY; PHYSIOLOGY;

ATAXIA; BRAIN; CALCIUM; CALCIUM CHANNELS, N-TYPE; CHILD; HUMANS; MAGNETIC RESONANCE IMAGING; MALE; NEUROIMAGING; SEQUENCE DELETION;

EID: 84957600854     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0146035     Document Type: Article

References (79)

1. Catterall WA. Voltage-gated calcium channels. Cold Spring Harb Perspect Biol. 2011; 3: A003947. doi: 10.1101/cshperspect.a003947 PMID: 21746798.
2. Serra SA, Cuenca-León E, Llobet A, Rubio-Moscardo F, Plata C, Carreño O, et al. A mutation in the first intracellular loop of CACNA1A prevents P/Q channel modulation by SNARE proteins and lowers exocytosis. Proc Natl Acad Sci USA. 2010; 107: 1672-1677. doi: 10.1073/pnas.0908359107 PMID: 20080591.
3. Westenbroek RE, Sakurai T, Elliott EM, Hell JW, Starr TV, Snutch TP, et al. Immunochemical identification and sub cellular distribution of the α1A subunits of brain calcium channels. J Neurosci. 1995; 15: 6403-6418. PMID: 7472404.
4. Pineda JC, Waters RS, Foehring RC. Specificity in the interaction of HVA Ca2+ channel types with Ca2+-dependent AHPs and firing behavior in neocortical pyramidal neurons. J Neurophysiol. 1998; 79: 2522-2534. PMID: 9582225.
5. Womack MD, Chevez C, Khodakhah K. Calcium activated potassium channels are selectively coupled to P/Q type calcium channels in cerebellar Purkinje neurons. J Neurosci. 2004; 24: 8818-8822. PMID: 15470147.
6. Gao Z, Todorov B, Barrett CF, van Dorp S, Ferrari MD, van den Maagdenberg AMJM, et al. Cerebellar ataxia by enhanced CaV2.1 currents is alleviated by Ca2+-dependent K+-channel activators in CACNA1AS218L mutant mice. J Neurosci. 2012; 32: 15533-15546. doi: 10.1523/JNEUROSCI.2454-12.2012 PMID: 23115190.
7. Sutton KG, McRory JE, Guthrie H, Murphy TH, Snutch TP. P/Q-type calcium channels mediate the activity-dependent feedback of syntaxin-1A. Nature. 1999; 401: 800-804. PMID: 10548106.
8. Eilers J, Plant T, Konnerth A. Localized calcium signaling and neuronal integration in cerebellar Purkinje neurones. Cell Calcium. 1996; 20: 215-226. PMID: 8889210.
9. Fletcher CF, Tottene A, Lennon VA, Wilson SM, Dubel SJ, Paylor R, et al. Dystonia and cerebellar atrophy in Cacna1a null mice lacking P/Q calcium channel activity. FASEB J. 2001; 15: 1288-1290. PMID: 11344116.
10. Pietrobon D, Striessnig J. Neurobiology of migraine. Nat Rev Neurosci. 2003; 4: 386-398. PMID: 12728266.
11. Pietrobon D. CaV2.1 channelopathies. Pflügers Arch-Eur J Physiol. 2010; 460: 375-393.
12. Pelzer N, Stam AH, Haan J, Ferrari MD, Terwindt GM. Familial and sporadic hemiplegic migraine: diagnosis and treatment. Curr Treat Options Neurol. 2013; 15: 13-27. doi: 10.1007/s11940-012-0208-3 PMID: 23203776.
13. Serra SA, Fernàndez-Castillo N, Macaya A, Cormand B, Valverde MA, Fernández-Fernández JM. The Hemiplegic Migraine associated Y1245C mutation in CACNA1A results in a gain of channel function due to its effect on the voltage sensor and G-protein mediated inhibition. Pflügers Arch-Eur J Physiol. 2009; 458: 489-502.
14. Carreño O, Corominas R, Serra SA, Sintas C, Fernández-Castillo N, Vila-Pueyo M, et al. Screening of CACNA1A and ATP1A2 genes in hemiplegic migraine: clinical, genetic, and functional studies. Mol Genet & Genomic Med. 2013; 1: 206-222.
15. Vecchia D, Tottene A, van den Maagdenberg AMJM, Pietrobon D. Mechanism underlying unaltered cortical inhibitory synaptic transmission in contrast with enhanced excitatory transmission in CaV2.1 knockin migraine mice. Neurobiol Dis. 2014; 69: 225-234. doi: 10.1016/j.nbd.2014.05.035 PMID: 24907493.
16. van den Maagdenberg AMJM, Pietrobon D, Pizzorusso T, Kaja S, Broos LA, Cesetti T, et al. A Cacna1a knockin migraine mouse model with increased susceptibility to cortical spreading depression. Neuron. 2004; 41: 701-710. PMID: 15003170.
17. Tottene A, Conti R, Fabbro A, Vecchia D, Shapovalova M, Santello M, et al. Enhanced excitatory transmission at cortical synapses as the basis for facilitated spreading depression in CaV2.1 knockin migraine mice. Neuron. 2009; 61: 762-773. doi: 10.1016/j.neuron.2009.01.027 PMID: 19285472.
18. Di Guilmi MN, Wang T, Inchauspe CG, Forsythe ID, Ferrari MD, van den Maagdenberg AMJM, et al. Synaptic gain-of-function effects of mutant CaV2.1 channels in a mouse model of familial hemiplegic migraine are due to increased basal [Ca2+]i. J Neurosci. 2014; 34: 7047-7058. doi: 10.1523/JNEUROSCI.2526-13.2014 PMID: 24849341.
19. Bolay H, Reuter U, Dunn AK, Huang Z, Boas DA, Moskowitz MA. Intrinsic brain activity triggers trigeminal meningeal afferents in a migraine model. Nat Med. 2002; 8: 136-142. PMID: 11821897.
20. Pietrobon D, Moskowitz MA. Pathophysiology of migraine. Annu Rev Physiol. 2013; 75: 365-391. doi: 10.1146/annurev-physiol-030212-183717 PMID: 23190076.
21. Cuenca-León E, Banchs I, Serra SA, Latorre P, Fernàndez-Castillo N, Corominas R, et al. Late-Onset Episodic Ataxia Type 2 associated with a novel loss-of-function mutation in the CACNA1A gene. J Neurol Sci. 2009; 28: 10-14.
22. Strupp M, Zwergal A, Brandt T. Episodic ataxia type 2. Neurotherapeutics. 2007; 4: 267-273. PMID: 17395137.
23. Scoggan KA, Friedman JH, Bulman DE. CACNA1A mutation in a EA-2 patient responsive to acetazolamide and valproic acid. Can J Neurol Sci. 2006; 33: 68-72. PMID: 16583725.
24. Rajakulendran S, Graves TD, Labrum RW, Kotzadimitriou D, Eunson L, Davis MB, et al. Genetic and functional characterisation of the P/Q calcium channel in episodic ataxia with epilepsy. J Physiol. 2010; 588: 1905-1913. doi: 10.1113/jphysiol.2009.186437 PMID: 20156848.
25. Imbrici P, Jaffe SL, Eunson LH, Davies NP, Herd C, Robertson R, et al. Dysfunction of the brain calcium channel CaV2.1 in absence epilepsy and episodic ataxia. Brain. 2004; 127: 2682-2692. PMID: 15483044.
26. Vila-Pueyo M, Gené GG, Flotats-Bastardes M, Elorza X, Sintas C, Valverde MA, et al. A loss-of-function CACNA1A mutation causing benign paroxysmal torticollis of infancy. Eur J Paediatr Neurol. 2014; 18: 430-433. doi: 10.1016/j.ejpn.2013.12.011 PMID: 24445160.
27. Mori Y, Wakamori M, Oda S, Fletcher CF, Sekiguchi N, Mori E, et al. Reduced voltage sensitivity of activation of P/Q-type Ca2+ channels is associated with the ataxic mouse mutation Rolling Nagoya (tgrol). J Neurosci. 2000; 20: 5654-5662. PMID: 10908603.
28. Imbrici P, Eunson LH, Graves TD, Bhatia KP, Wadia NH, Kullmann DM, et al. Late-onset episodic ataxia type 2 due to an in-frame insertion in CACNA1A. Neurology. 2005; 65: 944-946. PMID: 16186543.
29. Spacey SD, Hildebrand ME, Materek LA, Bird TD, Snutch TP. Functional implications of a novel EA2 mutation in the P/Q-type calcium channel. Ann Neurol. 2004; 56: 213-220. PMID: 15293273.
30. Wan J, Khanna R, Sandusky M, Papazian DM, Jen JC, Baloh RW. CACNA1A mutations causing episodic and progressive ataxia alter channel trafficking and kinetics. Neurology. 2005; 64: 2090-2097. PMID: 15985579.
31. Wappl E, Koschak A, Poteser M, Sinnegger MJ, Walter D, Eberhart A, et al. Functional consequences of P/Q-type Ca2+ channel CaV2.1 missense mutations associated with episodic ataxia type 2 and progressive ataxia. J Biol Chem. 2002; 277: 6960-6966. PMID: 11742003.
32. Cricchi F, Di Lorenzo C, Grieco GS, Rengo C, Cardinale A, Racaniello M, et al. Early-onset progressive ataxia associated with the first CACNA1A mutation identified within the I-II loop. J Neurol Sci. 2007; 254: 69-71. PMID: 17292920.
33. Rose SJ, Kriener LH, Heinzer AK, Fan X, Raike RS, van den Maagdenberg AMJM, et al. The first knockin mouse model of episodic ataxia type 2. Exp Neurol. 2014; 261C: 553-562.
34. Zhuchenko O, Bailey J, Bonnen P, Ashizawa T, Stockton DW, Amos C, et al. Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the α1A-voltage-dependent calcium channel. Nature Genet. 1997; 15: 62-69. PMID: 8988170.
35. Watase K, Barrett CF, Miyazaki T, Ishiguro T, Ishikawa K, Hu Y, et al. Spinocerebellar ataxia type 6 knock in mice develop a progressive neuronal dysfunction with age-dependent accumulation of mutant CaV2.1 channels. Proc Natl Acad Sci USA. 2008; 105: 11987-11992. doi: 10.1073/pnas.0804350105 PMID: 18687887.
36. Fitzsimons RB, Wolfenden WH. Migraine coma: meningitic migraine with cerebral oedema associated with a new form of autosomal dominant cerebellar ataxia. Brain. 1985; 108: 555-577. PMID: 4041774.
37. Kors EE, Terwindt GM, Vermeulen FL, Fitzsimons RB, Jardine PE, Heywood P, et al. Delayed cerebral edema and fatal coma after minor head trauma: role of the CACNA1A calcium channel subunit gene and relationship with familial hemiplegic migraine. Ann Neurol. 2001; 49: 753-760. PMID: 11409427.
38. Terwindt GM, Ophoff RA, Haan J, Vergouwe MN, van Eijk R, Frants RR, et al. Variable clinical expression of mutations in the P/Q-type calcium channel gene in familial hemiplegic migraine. Dutch Migraine Genetics Research Group. Neurology. 1998; 50: 1105-1110. PMID: 9566402.
39. Ducros A, Denier C, Joutel A, Vahedi K, Michel A, Darcel F, et al. Recurrence of the T666M calcium channel CACNA1A gene mutation in familial hemiplegic migraine with progressive cerebellar ataxia. Am J Hum Genet. 1999; 64:89-98. PMID: 9915947.
40. Wada T, Kobayashi N, Takahashi Y, Aoki T, Watanabe T, Saitoh S. Wide clinical variability in a family with a CACNA1A T666M mutation. Hemiplegic coma and progressive ataxia. Pediatr Neurol. 2002; 26: 47-50. PMID: 11814735.
41. Blumkin L, Michelson M, Leshinsky-Silver E, Kivity S, Lev D, Lerman-Sagie T. Congenital ataxia, mental retardation, and dyskinesia associated with a novel CACNA1A mutation. J Child Neurol. 2010; 25:892-7. doi: 10.1177/0883073809351316 PMID: 20097664.
42. Knierim E, Leisle L, Wagner C, Weschke B, Lucke B, Bohner G, et al. Recurrent stroke due to a novel voltage sensor mutation in CaV2.1 responds to verapamil. Stroke. 2011; 42: 14-7. doi: 10.1161/STROKEAHA.110.600023 PMID: 21183743.
43. Naik S, Pohl K, Malik M, Siddiqui A, Josifova D. Early-onset cerebellar atrophy associated with mutation in the CACNA1A gene. Pediatr Neurol. 2011; 45: 328-330. doi: 10.1016/j.pediatrneurol.2011.08.002 PMID: 22000314.
44. García-Segarra N, Gautschi I, Mittaz-Crettol L, Kallay Zetchi C, Al-Qusairi L, Van Bemmelen MX, et al. Congenital ataxia and hemiplegic migraine with cerebral edema associated with a novel gain of function mutation in the calcium channel CACNA1A. J Neurol Sci. 2014; 342: 69-78. doi: 10.1016/j.jns.2014.04. 027 PMID: 24836863.
45. De Pristo MA, Banks E, Poplin R, Garimella KV, Maguire JR, Hartl C, et al. A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nat Genet. 2011; 43: 491-498. doi: 10.1038/ng.806 PMID: 21478889.
46. Li H. Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM. arXiv 2013; 1-3.
47. Ossowski S, Schneeberger K, Clark RM, Lanz C, Warthmann N, Weigel D. Sequencing of natural strains of Arabidopsis thaliana with short reads. Genome Res. 2008; 18: 2024-33. doi: 10.1101/gr. 080200.108 PMID: 18818371.
48. Wang K, Li M, Hakonarson H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 2010; 38: E164. doi: 10.1093/nar/gkq603 PMID: 20601685.
49. Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, et al. A method and server for predicting damaging missense mutations. Nat Methods. 2010; 7: 248-249. doi: 10.1038/nmeth0410-248 PMID: 20354512.
50. Ng PC, Henikoff S. SIFT: predicting amino acid changes that affect protein function. Nucleic Acids Res. 2003; 31: 3812-3814. PMID: 12824425.
51. González-Pérez A, López-Bigas N. Improving the assessment of the outcome of nonsynonymous SNVs with a consensus deleteriousness score, Condel. Am J Hum Genet. 2011; 88: 440-449. doi: 10. 1016/j.ajhg.2011.03.004 PMID: 21457909.
52. Kircher M, Witten DM, Jain P, ÓRoak BJ, Cooper GM, Shendure J. A general framework for estimating the relative pathogenicity of human genetic variants. Nat Genet. 2014; 46: 310-315. doi: 10.1038/ng. 2892 PMID: 24487276.
53. Margulies EH, Blanchette M, NISC Comparative Sequencing Program, Haussler D, Green ED. Identification and characterization of multi-species conserved sequences, Genome Res. 2003; 13: 2507-2518. PMID: 14656959.
54. Tranchevent LC, Barriot R, Yu S, Van Vooren S, Van Loo P, Coessens B, et al. ENDEAVOUR update: A web resource for gene prioritization in multiple species. Nucleic Acids Res. 2008; 36(Web Server issue): W377-W384. doi: 10.1093/nar/gkn325 PMID: 18508807.
55. Hamosh AA, Scott F, Amberger JS, Bocchini CA, McKusick VA. Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders. Nucleic Acids Res. 2005; 33(Database issue): D514-D517. PMID: 15608251.
56. Kaplan JC, Hamroun D. The 2014 version of the gene table of monogenic neuromuscular disorders (nuclear genome). Neuromuscul Disord. 2013; 23: 1081-1111. PMID: 24446552.
57. Pattillo JM, Artim DE, Simples JE Jr, Meriney SD. Variations in onset of action potential broadening: Effects on calcium current studied in chick ciliary ganglion neurones. J Physiol. 1999; 514: 719-728. PMID: 9882744.
58. Oelstrom K, Goldschen-Ohm MP, Holmgren M, Chanda B. Evolutionarily conserved intracellular gate of voltage-dependent sodium channels. Nat Commun. 2014; 5: 3420. doi: 10.1038/ncomms4420 PMID: 24619022.
59. Zhong H, Yokoyama CT, Scheuer T, Catterall WA. Reciprocal regulation of P/Q type Ca2+ channels by SNAP-25, syntaxin and synaptotagmin. Nat Neurosci. 1999; 2: 939-941. PMID: 10526329.
60. Kraus RL, Sinnegger MJ, Koschak A, Glossmann H, Stenirri S, Carrera P, et al. Three new familial hemiplegic migraine mutants affect P/Q-type Ca2+ channel kinetics. J Biol Chem. 2000; 275: 9239-9243. PMID: 10734061.
61. Pietrobon D. Familial hemiplegic migraine. Neurotherapeutics 2007; 4: 274-284. PMID: 17395138.
62. Tottene A, Pivotto F, Fellin T, Cesetti T, van den Maagdenberg AMJM, Pietrobon D. Specific kinetic alterations of human CaV2.1 calcium channels produced by mutation S218L causing familial hemiplegic migraine and delayed cerebral edema and coma after minor head trauma. J Biol Chem. 2005; 280: 17678-17686. PMID: 15743764.
63. Kraus RL, Sinnegger MJ, Glossmann H, Hering S, Striessnig J. Familial hemiplegic migraine mutations change α1A Ca2+ channel kinetics. J Biol Chem. 1998; 273: 5586-5590. PMID: 9488686.
64. Miki T, Zwingman TA, Wakamori M, Lutz CM, Cook SA, Hosford DA, et al. Two novel alleles of tottering with distinct CaV2.1 calcium channel neuropathologies. Neuroscience. 2008; 155:31-44. doi: 10.1016/j.neuroscience.2008.05.028 PMID: 18597946.
65. Fioretti B, Catacuzzeno L, Sforna L, Gerke-Duncan MB, van denMaagdenberg AMJM, Franciolini F, et al. Trigeminal ganglion neuron subtype-specific alterations of CaV2.1 calcium current and excitability in a Cacna1a mouse model of migraine. J Physiol. 2011; 589: 5879-5895. doi: 10.1113/jphysiol.2011. 220533 PMID: 22005682.
66. van den Maagdenberg AMJM, Pizzorusso T, Kaja S, Terpolilli N, Shapovalova M, Hoebeek FE, et al. High cortical spreading depression susceptibility and migraine-associated symptoms in CaV2.1 S218L mice. Ann Neurol. 2010; 67: 85-98. doi: 10.1002/ana.21815 PMID: 20186955.
67. Kasumu A, Bezprozvanny I. Deranged calcium signaling in Purkinje cells and pathogenesis in spinocerebellar ataxia 2 (SCA2) and other ataxias. Cerebellum. 2012; 11: 630-9. doi: 10.1007/s12311-010-0182-9 PMID: 20480274.
68. Turkmen S, Guo G, Garshasbi M, Hoffmann K, Alshalah AJ, Mischung C, et al. CA8 mutations cause a novel syndrome characterized by ataxia and mild mental retardation with predisposition to quadrupedal gait. PLoS Genet. 2009; 5(5): E1000487. doi: 10.1371/journal.pgen.1000487 PMID: 19461874.
69. Kaya N, Aldhalaan H, Al-Younes B, Colak D, Shuaib T, Al-Mohaileb F, et al. Phenotypical spectrum of cerebellar ataxia associated with a novel mutation in the CA8 gene, encoding carbonic anhydrase (CA) VIII. Am J Med Genet Part B. 2011; 156: 826-834.
70. Hirota J, Ando H, Hamada K, Mikoshiba K. Carbonic anhydrase-related protein is a novel binding protein for inositol 1, 4, 5-trisphosphate receptor type 1. Biochem J. 2003; 372: 435-441. PMID: 12611586.
71. Mikoshiba K. IP3 receptor/Ca2+ channel: from discovery to new signaling concepts. J Neurochem. 2007; 102: 1426-1446. PMID: 17697045.
72. Sotelo C, Hillman DE, Zamora AJ, Llinas R. Climbing fiber deafferentation: its action on Purkinje cell dendritic spines. Brain Res. 1975; 98: 574-581. PMID: 1182538.
73. Bravin M, Morando L, Vercelli A, Rossi F, Strata P. Control of spine formation by electrical activity in the adult rat cerebellum. Proc Natl Acad Sci USA. 1999; 96:1704-1709. PMID: 9990088.
74. Jiao Y, Yan J, Zhao Y, Donahue LR, Beamer WG, et al. Carbonic anhydrase-related protein VIII deficiency is associated with a distinctive lifelong gait disorder in waddles mice. Genetics. 2005; 171: 1239-1246. PMID: 16118194.
75. Hirasawa M, Xu X, Trask RB, Maddatu TP, Johnson BA, Naggert JK, et al. Carbonic anhydrase related protein 8 mutation results in aberrant synaptic morphology and excitatory synaptic function in the cerebellum. Mol Cell Neurosci. 2007; 35: 161-170. PMID: 17376701.
76. Aspatwar A, Tolvanen MEE, Jokitalo E, Parikka M, Ortutay C, Harjula S-KE, et al. Abnormal cerebellar development and ataxia in CARP VIII morphant zebrafish. Hum Mol Genet. 2013; 22: 417-432. doi: 10. 1093/hmg/dds438 PMID: 23087022.
77. Zanni G, Calì T, Kalscheuer VM, Ottolini D, Barresi S, Lebrun N, et al. Mutation of plasma membrane Ca2+ ATPase isoform 3 in a family with X-linked congenital cerebellar ataxia impairs Ca2+ homeostasis. Proc Natl Acad Sci USA. 2012; 109: 14514-14519. doi: 10.1073/pnas.1207488109 PMID: 22912398.
78. Inagaki A, Frank CA, Usachev YM, Benveniste M, Lee A. Pharmacological correction of gating defects in the voltage-gated CaV2.1 Ca2+ channel due to a Familial Hemiplegic Migraine mutation. Neuron. 2014; 81: 91-102. doi: 10.1016/j.neuron.2013.10.056 PMID: 24411734.
79. Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, et al. UCSF Chimera: A visualization system for exploratory research and analysis. J Comput Chem. 2004; 25: 1605-12. PMID: 15264254.