LGI proteins in the nervous system

ASN Neuro

Volumn 5, Issue 3, 2013, Pages 167-181

  Kegel, Linde ^a   Aunin, Eerik ^a   Meijer, Dies ^a   Bermingham, John R ^a,b,c  

^a ERASMUS MEDICAL CENTER   (Netherlands)

^b MCLAUGHLIN RESEARCH INSTITUTE   (United States)

^c WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Autosomal dominant lateral temporal (lobe) epilepsy (ADLTE); Autosomal dominant partial epilepsy with auditory features (ADPEAF); Epitempin; Leucine rich gliomainactivated protein; Leucine rich repeat (LRR); PNS development; Synapse

Indexed keywords

ADAM PROTEIN; ADAM11 PROTEIN; ADAM22 PROTEIN; ADAM23 PROTEIN; AMPA RECEPTOR; BRAIN PROTEIN; FLOTILLIN 1; LEUCINE RICH GLIOMA INACTIVATED PROTEIN; LGI1 PROTEIN; LGI2 PROTEIN; LGI3 PROTEIN; LGI4 PROTEIN; N METHYL DEXTRO ASPARTIC ACID; SYNTAXIN 1; UNCLASSIFIED DRUG;

AUTOSOMAL DOMINANT DISORDER; CELL INTERACTION; CELL PROLIFERATION; CENTRAL NERVOUS SYSTEM; CHROMOSOME TRANSLOCATION; GENE IDENTIFICATION; GENE MUTATION; GLIA CELL; GLIOMA; HUMAN; LATERAL TEMPORAL LOBE EPILEPSY; LGI GENE; MOLECULAR EVOLUTION; MYELINATION; NERVOUS SYSTEM DEVELOPMENT; NONHUMAN; PARANEOPLASTIC NEUROPATHY; PERIPHERAL NERVOUS SYSTEM; PROTEIN ANALYSIS; PROTEIN BINDING; PROTEIN DOMAIN; PROTEIN FAMILY; PROTEIN FUNCTION; PROTEIN PROCESSING; PROTEIN PROTEIN INTERACTION; PROTEIN SECRETION; PROTEIN STRUCTURE; REVIEW; SYNAPTIC TRANSMISSION;

EID: 84880364986     PISSN: 17590914     EISSN: None     Source Type: Journal    
DOI: 10.1042/AN20120095     Document Type: Review

References (136)

1. Amemiya C. T, Alf̈oldi J, Lee AP, Fan S, Philippe H, Maccallum I, Braasch I, Manousaki T., Schneider I, Rohner N et al. (2013) The African coelacanth genome provides insights into tetrapod evolution. Nature 496:311-316.
2. Barth A. L, Malenka RC (2001) NMDAR EPSC kinetics do not regulate the critical period for LTP at thalamocortical synapses. Nat Neurosci 4:235-236.
3. Baulac S., Ishida S, Mashimo T, Boillot M, Fumoto N, Kuwamura M, Ohno Y, Takizawa A., Aoto T, Ueda M, Ikeda A, LeGuern E, Takahashi R, Serikawa T (2012) A rat model for LGI1-related epilepsies. Human molecular genetics 21:3546-3557.
4. Berghuis B., Brilstra EH, Lindhout D, Baulac S, de Haan GJ, van Kempen M (2013) Hyperactive behavior in a family with autosomal dominant lateral temporal lobe epilepsy caused by a mutation in the LGI1/epitempin gene. Epilepsy & behavior: E&B 28:41-46.
5. Bermingham Jr, JR, Scherer SS, O'Connell S, Arroyo E, Kalla KA, Powell FL, Rosenfeld M. G (1996) Tst-1/Oct-6/SCIP regulates a unique step in peripheral myelination and is required for normal respiration. Genes Dev 10:1751-1762.
6. Bermingham Jr, JR, Shearin H, Pennington J, O'Moore J, Jaegle M, Driegen S, van Zon A, Darbas A, ̈ Ozkaynak E, Ryu EJ, Milbrandt J, Meijer D (2006) The claw paw mutation reveals a role for Lgi4 in peripheral nerve development. Nat Neurosci 9:76-84.
7. Besleaga R., Montesinos-Rongen M, Perez-Tur J, Siebert R, Deckert M (2003) Expression of the LGI1 gene product in astrocytic gliomas: downregulation with malignant progression. Virchows Arch 443:561-564.
8. Blobel C. P (2005) ADAMs: key components in EGFR signalling and development. Nat Rev Mol Cell Biol 6:32-43.
9. Brodtkorb E., Nakken KO, Steinlein OK (2003) No evidence for a seriously increased malignancy risk in LGI1-caused epilepsy. Epilepsy Res 56:205-208.
10. Buchanan S. G, Gay NJ (1996) Structural and functional diversity in the leucine-rich repeat family of proteins. Prog Biophys Mol Biol 65:1-44.
11. Chabrol E., Navarro V, Provenzano G, Cohen I, Dinocourt C, Rivaud-Pechoux S, Fricker D., Baulac M, Miles R, Leguern E, Baulac S (2010) Electroclinical characterization of epileptic seizures in leucine-rich, glioma-inactivated 1-deficient mice. Brain 133:2749-2762.
12. Chaudhuri I., Soding J, Lupas AN (2008) Evolution of the beta-propeller fold. Proteins 71:795-803.
13. Chavis P., Westbrook G (2001) Integrins mediate functional pre-and postsynaptic maturation at a hippocampal synapse. Nature 411:317-321.
14. Chen L., Chetkovich DM, Petralia RS, Sweeney NT, Kawasaki Y, Wenthold RJ, Bredt D. S, Nicoll RA (2000) Stargazin regulates synaptic targeting of AMPA receptors by two distinct mechanisms. Nature 408:936-943.
15. Chernova O. B, Somerville RP, Cowell JK (1998) A novel gene, LGI1, from 10q24 is rearranged and downregulated in malignant brain tumors. Oncogene 17:2873-2881.
16. Cowell J. K, Head K, Kunapuli P, Vaughan M, Karasik E, Foster B (2010) Inactivation of LGI1 expression accompanies early stage hyperplasia of prostate epithelium in the TRAMP murine model of prostate cancer. Exp Mol Pathol 88:77-81.
17. D'Abaco GM, Ng K, Paradiso L, Godde NJ, Kaye A, Novak U (2006) ADAM22, expressed in normal brain but not in high-grade gliomas, inhibits cellular proliferation via the disintegrin domain. Neurosurgery 58:179-186, discussion 179-186.
18. D'Antonio M, Musner N, Scapin C, Ungaro D, Del Carro U, Ron D, Feltri ML, Wrabetz L. (2013) Resetting translational homeostasis restores myelination in Charcot-Marie-Tooth disease type 1B mice. J Exp Med 210:821-838.
19. Darbas A., Jaegle M, Walbeehm E, van den Burg H, Driegen S, Broos L, Uyl M, Visser P., Grosveld F, Meijer D (2004) Cell autonomy of the mouse claw paw mutation. Dev Biol 272:470-482.
20. de Bellescize J, Boutry N, Chabrol E, Andre-Obadia N, Arzimanoglou A, Leguern E., Baulac S, Calender A, Ryvlin P, Lesca G (2009) A novel three base-pair LGI1 deletion leading to loss of function in a family with autosomal dominant lateral temporal epilepsy and migraine-like episodes. Epilepsy Res 85:118-122.
21. Dehal P., Boore JL (2005) Two rounds of whole genome duplication in the ancestral vertebrate. PLoS Biol 3:e314.
22. Delmaghani S., Aghaie A, Michalski N, Bonnet C, Weil D, Petit C (2012) Defect in the gene encoding the EAR/EPTP domain-containing protein TSPEAR causes DFNB98 profound deafness. Hum Mol Genet 21:3835-3844.
23. Dhaunchak A. S, Huang JK, De Faria Junior O, Roth AD, Pedraza L, Antel JP, Bar-Or A, Colman DR (2010) A proteome map of axoglial specializations isolated and purified from human central nervous system. Glia 58:1949-1960.
24. Di Bonaventura C, Operto FF, Busolin G, Egeo G, D'Aniello A, Vitello L, Smaniotto G., Furlan S, Diani E, Michelucci R, Giallonardo AT, Coppola G, Nobile C. (2011) Low penetrance and effect on protein secretion of LGI1 mutations causing autosomal dominant lateral temporal epilepsy. Epilepsia 52:1258-1264.
25. Doretto M. C, Cortes-de-Oliveira JA, Rossetti F, Garcia-Cairasco N (2009) Role of the superior colliculus in the expression of acute and kindled audiogenic seizures in Wistar audiogenic rats. Epilepsia 50:2563-2574.
26. Fukata Y., Adesnik H, Iwanaga T, Bredt DS, Nicoll RA, Fukata M (2006) Epilepsy-related ligand/receptor complex LGI1 and ADAM22 regulate synaptic transmission. Science 313:1792-1795.
27. Fukata Y., Lovero KL, Iwanaga T, Watanabe A, Yokoi N, Tabuchi K, Shigemoto R, Nicoll RA, Fukata M (2010) Disruption of LGI1-linked synaptic complex causes abnormal synaptic transmission and epilepsy. Proc Natl Acad Sci USA 107:3799-3804.
28. Fulop V., Jones DT (1999) Beta propellers: structural rigidity and functional diversity. Curr Opin Struct Biol 9:715-721.
29. Gabellini N., Masola V, Quartesan S, Oselladore B, Nobile C, Michelucci R, Curtarello M., Parolin C, Palu G (2006) Increased expression of LGI1 gene triggers growth inhibition and apoptosis of neuroblastoma cells. J Cell Physiol 207:711-721.
30. Garcia-Cairasco N (2002) A critical review on the participation of inferior colliculus in acoustic-motor and acoustic-limbic networks involved in the expression of acute and kindled audiogenic seizures. Hear Res 168:208-222.
31. Garcia-Cairasco N, Terra VC, Doretto MC (1993) Midbrain substrates of audiogenic seizures in rats. Behav Brain Res 58:57-67.
32. Gillis W. Q, St John J, Bowerman B, Schneider SQ (2009) Whole genome duplications and expansion of the vertebrate GATA transcription factor gene family. BMC Evol Biol 9:207.
33. Gu W., Wevers A, Schroder H, Grzeschik KH, Derst C, Brodtkorb E, de Vos R, Steinlein O. K (2002) The LGI1 gene involved in lateral temporal lobe epilepsy belongs to a new subfamily of leucine-rich repeat proteins. FEBS Lett 519:71-76.
34. Gu W., Brodtkorb E, Piepoli T, Finocchiaro G, Steinlein OK (2005a) LGI1: a gene involved in epileptogenesis and glioma progression? Neurogenetics 6:59-66.
35. Gu W., Gibert Y, Wirth T, Elischer A, Bloch W, Meyer A, Steinlein OK, Begemann G. (2005b) Using gene-history and expression analyses to assess the involvement of LGI genes in human disorders. Mol Biol Evol 22:2209-2216.
36. Han K., Kim E (2008) Synaptic adhesion molecules and PSD-95. Prog Neurobiol 84:263-283.
37. Head K., Gong S, Joseph S, Wang C, Burkhardt T, Rossi MR, LaDuca J, Matsui S, Vaughan M., Hicks DG, Heintz N, Cowell JK (2007) Defining the expression pattern of the LGI1 gene in BAC transgenic mice. Mamm Genome 18:328-337.
38. Heiman G. A, Kamberakis K, Gill R, Kalachikov S, Pedley TA, Hauser WA, Ottman R (2010) Evaluation of depression risk in LGI1 mutation carriers. Epilepsia 51:1685-1690.
39. Hellsten U., Harland RM, Gilchrist MJ, Hendrix D, Jurka J, Kapitonov V, Ovcharenko I., Putnam NH, Shu S, Taher L et al. (2010) The genome of the Western clawed frog Xenopus tropicalis. Science 328:633-636.
40. Henry E. W, Eicher EM, Sidman RL (1991) The mouse mutation claw paw: forelimb deformity and delayed myelination throughout the peripheral nervous system. J Hered 82:287-294.
41. Ho Y. Y, Ionita-Laza I, Ottman R (2012) Domain-dependent clustering and genotype-phenotype analysis of LGI1 mutations in ADPEAF. Neurology 78:563-568.
42. Howitt J. A, Clout NJ, Hohenester E (2004) Binding site for Robo receptors revealed by dissection of the leucine-rich repeat region of Slit. EMBO J 23:4406-4412.
43. Irani S. R, Vincent A (2011) Autoimmune encephalitis-new awareness, challenging questions. Discovery Med 11:449-458.
44. Irani S. R, Alexander S, Waters P, Kleopa KA, Pettingill P, Zuliani L, Peles E, Buckley C., Lang B, Vincent A (2010) Antibodies to Kv1 potassium channel-complex proteins leucine-rich, glioma inactivated 1 protein and contactin-associated protein-2 in limbic encephalitis, Morvan's syndrome and acquired neuromyotonia. Brain 133:2734-2748.
45. Irani S. R, Michell AW, Lang B, Pettingill P, Waters P, Johnson MR, Schott JM, Armstrong R. J, A SZ, Bleasel A, Somerville ER, Smith SM, Vincent A (2011) Faciobrachial dystonic seizures precede Lgi1 antibody limbic encephalitis. Ann Neurol 69:892-900.
46. Jaegle M., Mandemakers W, Broos L, Zwart R, Karis A, Visser P, Grosveld F, Meijer D. (1996) The POU factor Oct-6 and Schwann cell differentiation. Science 273:507-510.
47. Jawad Z., Paoli M (2002) Novel sequences propel familiar folds. Structure 10:447-454.
48. Jessen K. R (2004) Glial cells. Int J Biochem Cell Biol 36:1861-1867.
49. Jokinen T. S, Metsahonkala L, Bergamasco L, Viitmaa R, Syrja P, Lohi H, Snellman M., Jeserevics J, Cizinauskas S (2007) Benign familial juvenile epilepsy in Lagotto Romagnolo dogs. J Vet Int Med 21:464-471.
50. Kalachikov S., Evgrafov O, Ross B, Winawer M, Barker-Cummings C, Martinelli Boneschi F., Choi C, Morozov P, Das K, Teplitskaya E, Yu A, Cayanis E, Penchaszadeh G., Kottmann AH, Pedley TA, Hauser WA, Ottman R, Gilliam TC (2002) Mutations in LGI1 cause autosomal-dominant partial epilepsy with auditory features. Nat Genet 30:335-341.
51. Kawamata J., Ikeda A, Fujita Y, Usui K, Shimohama S, Takahashi R (2010) Mutations in LGI1 gene in Japanese families with autosomal dominant lateral temporal lobe epilepsy: the first report from Asian families. Epilepsia 51:690-693.
52. Kim H. A, Park WJ, Jeong HS, Lee HE, Lee SH, Kwon NS, Baek KJ, Kim DS, Yun HY (2012) Leucine-rich glioma inactivated 3 regulates adipogenesis through ADAM23. Biochim Biophys Acta 1821:914-922.
53. Kim H. A, Kwon NS, Baek KJ, Kim DS, Yun HY (2013) Leucine-rich glioma inactivated 3 associates negatively with adiponectin. Cytokine 62:206-209.
54. Kimura N., Ishii Y, Suzaki S, Negishi T, Kyuwa S, Yoshikawa Y (2007) Abeta upregulates and colocalizes with LGI3 in cultured rat astrocytes. Cell Mol Neurobiol 27:335-350.
55. Kobayashi E., Santos NF, Torres FR, Secolin R, Sardinha LA, Lopez-Cendes I, Cendes F. (2003) Magnetic resonance imaging abnormalities in familial temporal lobe epilepsy with auditory auras. Arch Neurol 60:1546-1551.
56. Kobe B., Kajava AV (2001) The leucine-rich repeat as a protein recognition motif. Curr Opin Struct Biol 11:725-732.
57. Krex D., Hauses M, Appelt H, Mohr B, Ehninger G, Schackert HK, Schackert G (2002) Physical and functional characterization of the human LGI1 gene and its possible role in glioma development. Acta Neuropathol 103:255-266.
58. Kunapuli P., Chitta KS, Cowell JK (2003) Suppression of the cell proliferation and invasion phenotypes in glioma cells by the LGI1 gene. Oncogene 22:3985-3991.
59. Kunapuli P., Kasyapa CS, Hawthorn L, Cowell JK (2004) LGI1, a putative tumor metastasis suppressor gene, controls in vitro invasiveness and expression of matrix metalloproteinases in glioma cells through the ERK1/2 pathway. J Biol Chem 279:23151-23157.
60. Kunapuli P., Lo K, Hawthorn L, Cowell JK (2010) Reexpression of LGI1 in glioma cells results in dysregulation of genes implicated in the canonical axon guidance pathway. Genomics 95:93-100.
61. Kusuzawa S., Honda T, Fukata Y, Fukata M, Kanatani S, Tanaka DH, Nakajima K. (2012) Leucine-rich glioma inactivated 1 (Lgi1), an epilepsy-related secreted protein, has a nuclear localization signal and localizes to both the cytoplasm and the nucleus of the caudal ganglionic eminence neurons. Eur J Neurosci 36:2284-2292.
62. Lai M., Huijbers MG, Lancaster E, Graus F, Bataller L, Balice-Gordon R, Cowell JK, Dalmau J (2010) Investigation of LGI1 as the antigen in limbic encephalitis previously attributed to potassium channels: a case series. Lancet Neurol 9:776-785.
63. Lalic T., Pettingill P, Vincent A, Capogna M (2011) Human limbic encephalitis serum enhances hippocampal mossy fiber-CA3 pyramidal cell synaptic transmission. Epilepsia 52:121-131.
64. Lee S. E, Lee AY, Park WJ, Jun DH, Kwon NS, Baek KJ, Kim YG, Yun HY (2006) Mouse LGI3 gene: expression in brain and promoter analysis. Gene 372:8-17.
65. Lee S. H, Jeong YM, Kim SY, Jeong HS, Park KC, Baek KJ, Kwon NS, Yun HY, Kim DS (2012) Ultraviolet B-induced LGI3 secretion protects human keratinocytes. Exp Dermatol 21:716-718.
66. Leonardi E., Andreazza S, Vanin S, Busolin G, Nobile C, Tosatto SC (2011) A computational model of the LGI1 protein suggests a common binding site for ADAM proteins. PLoS ONE 6:e18142.
67. Li S., Yang Z, Hu J, Gordon WC, Bazan NG, Haas AL, Bok D, Jin M (2013) Secretory defect and cytotoxicity: the potential disease mechanisms for the retinitis pigmentosa (RP)-associated interphotoreceptor retinoid-binding protein (IRBP). J Biol Chem 288:11395-11406.
68. Limviphuvadh V., Chua LL, Rahim RA, Eisenhaber F, Maurer-Stroh S, Adhikari S (2010) Similarity of molecular phenotype between known epilepsy gene LGI1 and disease candidate gene LGI2. BMC Biochem 11:39.
69. Magdaleno S., Jensen P, Brumwell CL, Seal A, Lehman K, Asbury A, Cheung T, Cornelius T., Batten DM, Eden C, Norland SM, Rice DS, Dosooye N, Shakya S, Mehta P, Curran T (2006) BGEM: an in situ hybridization database of gene expression in the embryonic and adult mouse nervous system. PLoS Biol 4:e86.
70. Manning G., Scheeff E (2010) How the vertebrates were made: selective pruning of a double-duplicated genome. BMC Biol 8:144.
71. McMahon SA, Diaz E (2011) Mechanisms of excitatory synapse maturation by trans-synaptic organizing complexes. Curr Opin Neurobiol 21:221-227.
72. McMillan DR, White PC (2004) Loss of the transmembrane and cytoplasmic domains of the very large G-protein-coupled receptor-1 (VLGR1 or Mass1) causes audiogenic seizures in mice. Mol Cell Neurosci 26:322-329.
73. Michelucci R., Pasini E, Malacrida S, Striano P, Bonaventura CD, Pulitano P, Bisulli F., Egeo G, Santulli L, Sofia V, Gambardella A, Elia M, de Falco A, Neve A. L, Banfi P, Coppola G, Avoni P, Binelli S, Boniver C, Pisano T, Marchini M., Dazzo E, Fanciulli M, Bartolini Y, Riguzzi P, Volpi L, de Falco FA, Giallonardo AT, Mecarelli O, Striano S, Tinuper P, Nobile C (2013) Low penetrance of autosomal dominant lateral temporal epilepsy in Italian families without LGI1 mutations. Epilepsia, in the press.
74. Morante-Redolat JM, Gorostidi-Pagola A, Piquer-Sirerol S, Śaenz A, Poza JJ, Gaĺan J, Gesk S, Sarafidou T, Mautner VF, Binelli S, Staub E, Hinzmann B, French L., Prud'homme JF, Passarelli D, Scannapieco P, Tassinari CA, Avanzini G., Mart́i{dotless}-Masśo JF, Kluwe L, Deloukas P, Moschonas NK, Michelucci R., Siebert R, Nobile C, Ṕerez-Tur J, Ĺopez de Munain A (2002) Mutations in the LGI1/Epitempin gene on 10q24 cause autosomal dominant lateral temporal epilepsy. Hum Mol Genet 11:1119-1128.
75. Nakayama J., Fu YH, Clark AM, Nakahara S, Hamano K, Iwasaki N, Matsui A, Arinami T., Ptacek LJ (2002) A nonsense mutation of the MASS1 gene in a family with febrile and afebrile seizures. Ann Neurol 52:654-657.
76. Nave K. A (2010) Myelination and support of axonal integrity by glia. Nature 468:244-252.
77. Nicoll R. A, Tomita S, Bredt DS (2006) Auxiliary subunits assist AMPA-type glutamate receptors. Science 311:1253-1256.
78. Nishino J., Saunders TL, Sagane K, Morrison SJ (2010) Lgi4 promotes the proliferation and differentiation of glial lineage cells throughout the developing peripheral nervous system. J Neurosci 30:15228-15240.
79. Nobile C., Michelucci R, Andreazza S, Pasini E, Tosatto SC, Striano P (2009) LGI1 mutations in autosomal dominant and sporadic lateral temporal epilepsy. Hum Mutat 30:530-536.
80. Ohno S. (1970) Evolution by gene duplication, Springer-Verlag, New York.
81. Okabayashi S., Kimura N (2007) Immunohistochemical and biochemical analyses of LGI3 in monkey brain: LGI3 accumulates in aged monkey brains. Cell Mol Neurobiol 27:819-830.
82. Okabayashi S., Kimura N (2008) Leucine-rich glioma inactivated 3 is involved in amyloid beta peptide uptake by astrocytes and endocytosis itself. NeuroReport 19:1175-1179.
83. Okabayashi S., Kimura N (2010) LGI3 interacts with flotillin-1 to mediate APP trafficking and exosome formation. Neuroreport 21:606-610.
84. Ottman R., Risch N, Hauser WA, Pedley TA, Lee JH, Barker-Cummings C, Lustenberger A., Nagle KJ, Lee KS et al. (1995) Localization of a gene for partial epilepsy to chromosome 10q. Nat Genet 10:56-60.
85. Owuor K., Harel NY, Englot DJ, Hisama F, Blumenfeld H, Strittmatter SM (2009) LGI1-associated epilepsy through altered ADAM23-dependent neuronal morphology. Mol Cell Neurosci 42:448-457.
86. ̈Ozkaynak E, Abello G, Jaegle M, van Berge L, Hamer D, Kegel L, Driegen S, Sagane K., Bermingham Jr, JR, Meijer D (2010) Adam22 is a major neuronal receptor for Lgi4-mediated Schwann cell signaling. J Neurosci 30:3857-3864.
87. Paoli M. (2001a) Protein folds propelled by diversity. Prog Biophys Mol Biol 76:103-130.
88. Paoli M. (2001b) An elusive propeller-like fold. Nat Struct Biol 8:744-745.
89. Park W. J, Lee SE, Kwon NS, Baek KJ, Kim DS, Yun HY (2008) Leucine-rich glioma inactivated 3 associates with syntaxin 1. Neurosci Lett 444:240-244.
90. Park W. J, Lim YY, Kwon NS, Baek KJ, Kim DS, Yun HY (2010) Leucine-rich glioma inactivated 3 induces neurite outgrowth through Akt and focal adhesion kinase. Neurochem Res 35:789-796.
91. Peng D., Sheta EA, Powell SM, Moskaluk CA, Washington K, Goldknopf IL, El-Rifai W (2008) Alterations in Barrett's-related adenocarcinomas: a proteomic approach. Int J Cancer 122:1303-1310.
92. Piaton G., Gould RM, Lubetzki C (2010) Axon-oligodendrocyte interactions during developmental myelination, demyelination and repair. J Neurochem 114:1243-1260.
93. Piepoli T., Jakupoglu C, Gu W, Lualdi E, Suarez-Merino B, Poliani PL, Cattaneo MG, Ortino B, Goplen D, Wang J, Mola R, Inverardi F, Frassoni C, Bjerkvig R, Steinlein O, Vicentini LM, Brustle O, Finocchiaro G (2006) Expression studies in gliomas and glial cells do not support a tumor suppressor role for LGI1. Neuro Oncol 8:96-108.
94. Plantone D., Renna R, Grossi D, Plantone F, Iorio R (2013) Teaching NeuroImages: basal ganglia involvement in facio-brachial dystonic seizures associated with LGI1 antibodies. Neurology 80:e183-e184.
95. Pons T., Gomez R, Chinea G, Valencia A (2003) Beta-propellers: associated functions and their role in human diseases. Curr Med Chem 10:505-524.
96. Poza J. J, Saenz A, Martinez-Gil A, Cheron N, Cobo AM, Urtasun M, Marti-Masso JF, Grid D, Beckmann JS, Prud'homme JF, Lopez de Munain A (1999) Autosomal dominant lateral temporal epilepsy: clinical and genetic study of a large Basque pedigree linked to chromosome 10q. Ann Neurol 45:182-188.
97. Quintes S., Goebbels S, Saher G, Schwab MH, Nave KA (2010) Neuron-glia signaling and the protection of axon function by Schwann cells. J Peripher Nerv Syst 15:10-16.
98. Ribeiro P. A, Sbragia L, Gilioli R, Langone F, Conte FF, Lopes-Cendes I (2008) Expression profile of Lgi1 gene in mouse brain during development. J Mol Neurosci 35:323-329.
99. Rosanoff M. J, Ottman R (2008) Penetrance of LGI1 mutations in autosomal dominant partial epilepsy with auditory features. Neurology 71:567-571.
100. Rossi M. R, Huntoon K, Cowell JK (2005) Differential expression of the LGI and SLIT families of genes in human cancer cells. Gene 356:85-90.
101. Roussel B. D, Kruppa AJ, Miranda E, Crowther DC, Lomas DA, Marciniak SJ (2013) Endoplasmic reticulum dysfunction in neurological disease. Lancet Neurol 12:105-118.
102. Sagane K., Hayakawa K, Kai J, Hirohashi T, Takahashi E, Miyamoto N, Ino M, Oki T., Yamazaki K, Nagasu T (2005) Ataxia and peripheral nerve hypomyelination in ADAM22-deficient mice. BMC Neurosci 6:33.
103. Sagane K., Ishihama Y, Sugimoto H (2008) LGI1 and LGI4 bind to ADAM22, ADAM23 and ADAM11. Int J Biol Sci 4:387-396.
104. Sagane K., Sugimoto H, Akaike A (2010) Biological characterization of ADAM22 variants reveals the importance of a disintegrin domain sequence in cell surface expression. J Recept Signal Transduct Res 30:72-77.
105. Scheel H., Tomiuk S, Hofmann K (2002) A common protein interaction domain links two recently identified epilepsy genes. Hum Mol Genet 11:1757-1762.
106. Schulte U., Thumfart JO, Klocker N, Sailer CA, Bildl W, Biniossek M, Dehn D, Deller T., Eble S, Abbass K, Wangler T, Knaus HG, Fakler B (2006) The epilepsy-linked Lgi1 protein assembles into presynaptic Kv1 channels and inhibits inactivation by Kvbeta1. Neuron 49:697-706.
107. Seals D. F, Courtneidge SA (2003) The ADAMs family of metalloproteases: multidomain proteins with multiple functions. Genes Dev 17:7-30.
108. Senechal K. R, Thaller C, Noebels JL (2005) ADPEAF mutations reduce levels of secreted LGI1, a putative tumor suppressor protein linked to epilepsy. Hum Mol Genet 14:1613-1620.
109. Sepp̈al̈a EH, Jokinen TS, Fukata M, Fukata Y, Webster MT, Karlsson EK, Kilpinen S. K, Steffen F, Dietschi E, Leeb T, Eklund R, Zhao X, Rilstone JJ, Lindblad-Toh K, Minassian BA, Lohi H (2011) LGI2 truncation causes a remitting focal epilepsy in dogs. PLoS Genet 7:e1002194.
110. Sepp̈al̈a EH, Koskinen LL, Gullov CH, Jokinen P, Karlskov-Mortensen P, Bergamasco L., Baranowska Korberg I, Cizinauskas S, Oberbauer AM, Berendt M., Fredholm M, Lohi H (2012) Identification of a novel idiopathic epilepsy locus in Belgian Shepherd dogs. PLoS ONE 7:e33549.
111. Siddiqui T. J, Craig AM (2011) Synaptic organizing complexes. Curr Opin Neurobiol 21:132-143.
112. Sirerol-Piquer MS, Ayerdi-Izquierdo A, Morante-Redolat JM, Herranz-Perez V, Favell K., Barker PA, Perez-Tur J (2006) The epilepsy gene LGI1 encodes a secreted glycoprotein that binds to the cell surface. Hum Mol Genet 15:3436-3445.
113. Skradski S. L, Clark AM, Jiang H, White HS, Fu YH, Ptacek LJ (2001) A novel gene causing a mendelian audiogenic mouse epilepsy. Neuron 31:537-544.
114. Staub E., Perez-Tur J, Siebert R, Nobile C, Moschonas NK, Deloukas P, Hinzmann B. (2002) The novel EPTP repeat defines a superfamily of proteins implicated in epileptic disorders. Trends Biochem Sci 27:441-444.
115. Striano P., Busolin G, Santulli L, Leonardi E, Coppola A, Vitiello L, Rigon L, Michelucci R., Tosatto SC, Striano S, Nobile C (2011) Familial temporal lobe epilepsy with psychic auras associated with a novel LGI1 mutation. Neurology 76:1173-1176.
116. Suga K., Yamamori T, Akagawa K (2003) Identification of the carboxyl-terminal membrane-anchoring region of HPC-1/syntaxin 1A with the substituted-cysteine-accessibility method and monoclonal antibodies. J Biochem 133:325-334.
117. Takahashi E., Sagane K, Nagasu T, Kuromitsu J (2006a) Altered nociceptive response in ADAM11-deficient mice. Brain Res 1097:39-42.
118. Takahashi E., Sagane K, Oki T, Yamazaki K, Nagasu T, Kuromitsu J (2006b) Deficits in spatial learning and motor coordination in ADAM11-deficient mice. BMC Neurosci 7:19.
119. Teng Y., Xie X, Walker S, Rempala G, Kozlowski DJ, Mumm JS, Cowell JK (2010) Knockdown of zebrafish Lgi1a results in abnormal development, brain defects and a seizure-like behavioral phenotype. Hum Mol Genet 19:4409-4420.
120. Teng Y., Xie X, Walker S, Saxena M, Kozlowski DJ, Mumm JS, Cowell JK (2011) Loss of zebrafish lgi1b leads to hydrocephalus and sensitization to pentylenetetrazol induced seizure-like behavior. PLoS ONE 6:e24596.
121. Tessa C., Michelucci R, Nobile C, Giannelli M, Della Nave R, Testoni S, Bianucci D, Tinuper P, Bisulli F, Sofia V, De Feo MR, Giallonardo AT, Tassinari CA, Mascalchi M. (2007) Structural anomaly of left lateral temporal lobe in epilepsy due to mutated LGI1. Neurology 69:1298-1300.
122. Thomas R., Favell K, Morante-Redolat J, Pool M, Kent C, Wright M, Daignault K, Ferraro GB, Montcalm S, Durocher Y, Fournier A, Perez-Tur J, Barker PA (2010) LGI1 is a Nogo receptor 1 ligand that antagonizes myelin-based growth inhibition. J Neurosci 30:6607-6612.
123. Tomita S., Adesnik H, Sekiguchi M, Zhang W, Wada K, Howe JR, Nicoll RA, Bredt D. S (2005) Stargazin modulates AMPA receptor gating and trafficking by distinct domains. Nature 435:1052-1058.
124. Tuzun E., Dalmau J (2007) Limbic encephalitis and variants: classification, diagnosis and treatment. Neurologist 13:261-271.
125. Van de Peer Y, Maere S, Meyer A (2009) The evolutionary significance of ancient genome duplications. Nat Rev Genet 10:725-732.
126. Vincent A., Bien CG, Irani SR, Waters P (2011) Autoantibodies associated with diseases of the CNS: new developments and future challenges. Lancet Neurol 10:759-772.
127. Waites C. L, Craig AM, Garner CC (2005) Mechanisms of vertebrate synaptogenesis. Annu Rev Neurosci 28:251-274.
128. Wang J., Valo Z, Bowers CW, Smith DD, Liu Z, Singer-Sam J (2010) Dual DNA methylation patterns in the CNS reveal developmentally poised chromatin and monoallelic expression of critical genes. PLoS ONE 5:e13843.
129. Winawer M. R, Ottman R, Hauser WA, Pedley TA (2000) Autosomal dominant partial epilepsy with auditory features: defining the phenotype. Neurology 54:2173-2176.
130. Winawer M. R, Martinelli Boneschi F, Barker-Cummings C, Lee JH, Liu J, Mekios C, Gilliam TC, Pedley TA, Hauser WA, Ottman R (2002) Four new families with autosomal dominant partial epilepsy with auditory features: clinical description and linkage to chromosome 10q24. Epilepsia 43:60-67.
131. Xu C., Min J (2011) Structure and function of WD40 domain proteins. Protein Cell 2:202-214.
132. Yang P., Baker KA, Hagg T (2006) The ADAMs family: coordinators of nervous system development, plasticity and repair. Prog Neurobiol 79:73-94.
133. Yokoi N., Fukata M, Fukata Y (2012) Synaptic plasticity regulated by protein-protein interactions and posttranslational modifications. Int Rev Cell Mol Biol 297:1-43.
134. Yu Y. E, Wen L, Silva J, Li Z, Head K, Sossey-Alaoui K, Pao A, Mei L, Cowell JK (2010) Lgi1 null mutant mice exhibit myoclonic seizures and CA1 neuronal hyperexcitability. Hum Mol Genet 19:1702-1711.
135. Zhou Y. D, Lee S, Jin Z, Wright M, Smith SE, Anderson MP (2009) Arrested maturation of excitatory synapses in autosomal dominant lateral temporal lobe epilepsy. Nat Med 15:1208-1214.
136. Zhou Y. D, Zhang D, Ozkaynak E, Wang X, Kasper EM, Leguern E, Baulac S, Anderson M. P (2012) Epilepsy gene LGI1 regulates postnatal developmental remodeling of retinogeniculate synapses. J Neurosci 32:903-910.