The LGI1 protein: molecular structure, physiological functions and disruption-related seizures.
AMPA receptors
Autoimmune encephalitis
Genetic epilepsy
Kv1
LGI1
Journal
Cellular and molecular life sciences : CMLS
ISSN: 1420-9071
Titre abrégé: Cell Mol Life Sci
Pays: Switzerland
ID NLM: 9705402
Informations de publication
Date de publication:
30 Dec 2021
30 Dec 2021
Historique:
received:
31
08
2021
accepted:
09
12
2021
revised:
07
12
2021
entrez:
30
12
2021
pubmed:
31
12
2021
medline:
12
1
2022
Statut:
epublish
Résumé
Leucine-rich, glioma inactivated 1 (LGI1) is a secreted glycoprotein, mainly expressed in the brain, and involved in central nervous system development and physiology. Mutations of LGI1 have been linked to autosomal dominant lateral temporal lobe epilepsy (ADLTE). Recently auto-antibodies against LGI1 have been described as the basis for an autoimmune encephalitis, associated with specific motor and limbic epileptic seizures. It is the second most common cause of autoimmune encephalitis. This review presents details on the molecular structure, expression and physiological functions of LGI1, and examines how their disruption underlies human pathologies. Knock-down of LGI1 in rodents reveals that this protein is necessary for normal brain development. In mature brains, LGI1 is associated with Kv1 channels and AMPA receptors, via domain-specific interaction with membrane anchoring proteins and contributes to regulation of the expression and function of these channels. Loss of function, due to mutations or autoantibodies, of this key protein in the control of neuronal activity is a common feature in the genesis of epileptic seizures in ADLTE and anti-LGI1 autoimmune encephalitis.
Identifiants
pubmed: 34967933
doi: 10.1007/s00018-021-04088-y
pii: 10.1007/s00018-021-04088-y
doi:
Substances chimiques
Intracellular Signaling Peptides and Proteins
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
16Subventions
Organisme : Agence nationale de la recherche, 'Investissements d'avenir' program
ID : ANR-10-IAIHU-06
Organisme : Fondation pour la Recherche Médicale
ID : FDT202012010523
Organisme : Fondation Assitance Publique-Hôpitaux de Paris
ID : EPIRES
Organisme : Fondation Assitance Publique-Hôpitaux de Paris
ID : Marie Laure PLV Merchandising
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
Références
Senechal KR, 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. https://doi.org/10.1093/hmg/ddi169
doi: 10.1093/hmg/ddi169
pubmed: 15857855
Fukata Y, Adesnik H, Iwanaga T et al (2006) Epilepsy-related ligand/receptor complex LGI1 and ADAM22 regulate synaptic transmission. Science 313:1792–1795. https://doi.org/10.1126/science.1129947
doi: 10.1126/science.1129947
pubmed: 16990550
Sirerol-Piquer MS, Ayerdi-Izquierdo A, Morante-Redolat JM et al (2006) The epilepsy gene LGI1 encodes a secreted glycoprotein that binds to the cell surface. Hum Mol Genet 15:3436–3445. https://doi.org/10.1093/hmg/ddl421
doi: 10.1093/hmg/ddl421
pubmed: 17067999
Dalmau J, Geis C, Graus F (2017) Autoantibodies to synaptic receptors and neuronal cell surface proteins in autoimmune diseases of the central nervous system. Physiol Rev 97:839–887. https://doi.org/10.1152/physrev.00010.2016
doi: 10.1152/physrev.00010.2016
pubmed: 28298428
Goodfellow JA, Mackay GA (2019) Autoimmune encephalitis. J R Coll Physicians Edinb 49:287–294. https://doi.org/10.4997/JRCPE.2019.407
doi: 10.4997/JRCPE.2019.407
pubmed: 31808454
Husari KS, Dubey D (2019) Autoimmune epilepsy. Neurotherapeutics 16:685–702. https://doi.org/10.1007/s13311-019-00750-3
doi: 10.1007/s13311-019-00750-3
pubmed: 31240596
Irani SR, Alexander S, Waters P et al (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. https://doi.org/10.1093/brain/awq213
doi: 10.1093/brain/awq213
pubmed: 20663977
Irani SR, Michell AW, Lang B et al (2011) Faciobrachial dystonic seizures precede Lgi1 antibody limbic encephalitis. Ann Neurol 69:892–900. https://doi.org/10.1002/ana.22307
doi: 10.1002/ana.22307
pubmed: 21416487
Lai M, Huijbers MG, Lancaster E et al (2010) Investigation of LGI1 as the antigen in limbic encephalitis previously attributed to potassium channels: a case series. Lancet Neurol 9:776–785. https://doi.org/10.1016/S1474-4422(10)70137-X
doi: 10.1016/S1474-4422(10)70137-X
pubmed: 20580615
Navarro V, Kas A, Apartis E et al (2016) Motor cortex and hippocampus are the two main cortical targets in LGI1-antibody encephalitis. Brain 139:1079–1093. https://doi.org/10.1093/brain/aww012
doi: 10.1093/brain/aww012
pubmed: 26945884
Pakozdy A, Patzl M, Zimmermann L et al (2015) LGI proteins and epilepsy in human and animals. J Vet Intern Med 29:997–1005. https://doi.org/10.1111/jvim.12610
doi: 10.1111/jvim.12610
pubmed: 26032921
Chernova OB, Somerville RP, Cowell JK (1998) A novel gene, LGI1, from 10q24 is rearranged and downregulated in malignant brain tumors. Oncogene 17:2873–2881. https://doi.org/10.1038/sj.onc.1202481
doi: 10.1038/sj.onc.1202481
pubmed: 9879993
Krex D, Hauses M, Appelt H et al (2002) Physical and functional characterization of the human LGI1 gene and its possible role in glioma development. Acta Neuropathol 103:255–266. https://doi.org/10.1007/s004010100463
doi: 10.1007/s004010100463
pubmed: 11907806
Besleaga R, Montesinos-Rongen M, Perez-Tur J et al (2003) Expression of the LGI1 gene product in astrocytic gliomas: downregulation with malignant progression. Virchows Arch 443:561–564. https://doi.org/10.1007/s00428-003-0874-3
doi: 10.1007/s00428-003-0874-3
pubmed: 12942323
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. https://doi.org/10.1038/sj.onc.1206584
doi: 10.1038/sj.onc.1206584
pubmed: 12821932
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. https://doi.org/10.1074/jbc.M314192200
doi: 10.1074/jbc.M314192200
pubmed: 15047712
Nadia G, Masola V, Quartesan S et al (2006) Increased expression ofLGI1 gene triggers growth inhibition and apoptosis of neuroblastoma cells. J Cell Physiol 207:711–721. https://doi.org/10.1002/jcp.20627
doi: 10.1002/jcp.20627
Piepoli T, Jakupoglu C, Gu W et al (2006) Expression studies in gliomas and glial cells do not support a tumor suppressor role for LGI11. Neuro Oncol 8:96–108. https://doi.org/10.1215/15228517-2005-006
doi: 10.1215/15228517-2005-006
pubmed: 16533756
Gu W, Brodtkorb E, Piepoli T et al (2005) LGI1: a gene involved in epileptogenesis and glioma progression? Neurogenetics 6:59–66. https://doi.org/10.1007/s10048-005-0216-5
doi: 10.1007/s10048-005-0216-5
pubmed: 15827762
Gadoth A, Pittock SJ, Dubey D et al (2017) Expanded phenotypes and outcomes among 256 LGI1/CASPR2-IgG-positive patients. Ann Neurol 82:79–92. https://doi.org/10.1002/ana.24979
doi: 10.1002/ana.24979
pubmed: 28628235
Somerville RPT, Chernova O, Liu S et al (2000) Identification of the promoter, genomic structure, and mouse ortholog of LGI1. Mamm Genome 11:622–627. https://doi.org/10.1007/s0033500101280
doi: 10.1007/s0033500101280
pubmed: 10920229
Chabrol E, Gourfinkel-An I, Scheffer IE et al (2007) Absence of mutations in the LGI1 receptor ADAM22 gene in autosomal dominant lateral temporal epilepsy. Epilepsy Res 76:41–48. https://doi.org/10.1016/j.eplepsyres.2007.06.014
doi: 10.1016/j.eplepsyres.2007.06.014
pubmed: 17681454
de Bellescize J, Boutry N, Chabrol E et al (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. https://doi.org/10.1016/j.eplepsyres.2009.02.007
doi: 10.1016/j.eplepsyres.2009.02.007
pubmed: 19268539
Head K, Gong S, Joseph S et al (2007) Defining the expression pattern of the LGI1 gene in BAC transgenic mice. Mamm Genome 18:328–337. https://doi.org/10.1007/s00335-007-9024-6
doi: 10.1007/s00335-007-9024-6
pubmed: 17565425
Gu W, Wevers A, Schröder H et al (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. https://doi.org/10.1016/S0014-5793(02)02713-8
doi: 10.1016/S0014-5793(02)02713-8
pubmed: 12023020
Yamagata A, Miyazaki Y, Yokoi N et al (2018) Structural basis of epilepsy-related ligand–receptor complex LGI1–ADAM22. Nat Commun 9:1546. https://doi.org/10.1038/s41467-018-03947-w
doi: 10.1038/s41467-018-03947-w
pubmed: 29670100
Scheel H (2002) A common protein interaction domain links two recently identified epilepsy genes. Hum Mol Genet 11:1757–1762. https://doi.org/10.1093/hmg/11.15.1757
doi: 10.1093/hmg/11.15.1757
pubmed: 12095917
Staub E, Pérez-Tur J, Siebert R et al (2002) The novel EPTP repeat defines a superfamily of proteins implicated in epileptic disorders. Trends Biochem Sci 27:441–444. https://doi.org/10.1016/S0968-0004(02)02163-1
doi: 10.1016/S0968-0004(02)02163-1
pubmed: 12217514
Leonardi E, Andreazza S, Vanin S et al (2011) A computational model of the LGI1 protein suggests a common binding site for ADAM proteins. PLoS ONE 6:e18142. https://doi.org/10.1371/journal.pone.0018142
doi: 10.1371/journal.pone.0018142
pubmed: 21479274
Kobe B, Kajava AV (2001) The leucine-rich repeat as a protein recognition motif. Curr Opin Struct Biol 11:725–732. https://doi.org/10.1016/s0959-440x(01)00266-4
doi: 10.1016/s0959-440x(01)00266-4
pubmed: 11751054
Silva J, Wang G, Cowell JK (2011) The temporal and spatial expression pattern of the LGI1 epilepsy predisposition gene during mouse embryonic cranial development. BMC Neurosci 12:43. https://doi.org/10.1186/1471-2202-12-43
doi: 10.1186/1471-2202-12-43
pubmed: 21569517
Boillot M, Huneau C, Marsan E et al (2014) Glutamatergic neuron-targeted loss of LGI1 epilepsy gene results in seizures. Brain 137:2984–2996. https://doi.org/10.1093/brain/awu259
doi: 10.1093/brain/awu259
pubmed: 25234641
Ohkawa T, Fukata Y, Yamasaki M et al (2013) Autoantibodies to epilepsy-related LGI1 in limbic encephalitis neutralize LGI1-ADAM22 interaction and reduce synaptic AMPA receptors. J Neurosci 33:18161–18174. https://doi.org/10.1523/JNEUROSCI.3506-13.2013
doi: 10.1523/JNEUROSCI.3506-13.2013
pubmed: 24227725
Kornau H, Kreye J, Stumpf A et al (2020) Human cerebrospinal fluid monoclonal LGI1 autoantibodies increase neuronal excitability. Ann Neurol 87:405–418. https://doi.org/10.1002/ana.25666
doi: 10.1002/ana.25666
pubmed: 31900946
Morante-Redolat JM (2002) Mutations in the LGI1/Epitempin gene on 10q24 cause autosomal dominant lateral temporal epilepsy. Hum Mol Genet 11:1119–1128. https://doi.org/10.1093/hmg/11.9.1119
doi: 10.1093/hmg/11.9.1119
pubmed: 11978770
Furlan S, Roncaroli F, Forner F et al (2006) The LGI1/epitempin gene encodes two protein isoforms differentially expressed in human brain. J Neurochem 98:985–991. https://doi.org/10.1111/j.1471-4159.2006.03939.x
doi: 10.1111/j.1471-4159.2006.03939.x
pubmed: 16787412
Chabrol E, Navarro V, Provenzano G et al (2010) Electroclinical characterization of epileptic seizures in leucine-rich, glioma-inactivated 1-deficient mice. Brain 133:2749–2762. https://doi.org/10.1093/brain/awq171
doi: 10.1093/brain/awq171
pubmed: 20659958
Xie Y-J, Zhou L, Wang Y et al (2018) Leucine-rich glioma inactivated 1 promotes oligodendrocyte differentiation and myelination via TSC-mTOR signaling. Front Mol Neurosci 11:231. https://doi.org/10.3389/fnmol.2018.00231
doi: 10.3389/fnmol.2018.00231
pubmed: 30034322
Kalachikov S, Evgrafov O, Ross B et al (2002) Mutations in LGI1 cause autosomal-dominant partial epilepsy with auditory features. Nat Genet 30:335–341. https://doi.org/10.1038/ng832
doi: 10.1038/ng832
pubmed: 11810107
Herranz-Pérez V, Olucha-Bordonau FE, Morante-Redolat JM, Pérez-Tur J (2010) Regional distribution of the leucine-rich glioma inactivated (LGI) gene family transcripts in the adult mouse brain. Brain Res 1307:177–194. https://doi.org/10.1016/j.brainres.2009.10.013
doi: 10.1016/j.brainres.2009.10.013
pubmed: 19833108
Smedfors G, Olson L, Karlsson TE (2018) A Nogo-like signaling perspective from birth to adulthood and in old age: brain expression patterns of ligands, receptors and modulators. Front Mol Neurosci 11:42. https://doi.org/10.3389/fnmol.2018.00042
doi: 10.3389/fnmol.2018.00042
pubmed: 29520216
Lovero KL, Fukata Y, Granger AJ et al (2015) The LGI1–ADAM22 protein complex directs synapse maturation through regulation of PSD-95 function. Proc Natl Acad Sci USA 112:E4129–E4137. https://doi.org/10.1073/pnas.1511910112
doi: 10.1073/pnas.1511910112
pubmed: 26178195
Boillot M, Lee C-Y, Allene C et al (2016) LGI1 acts presynaptically to regulate excitatory synaptic transmission during early postnatal development. Sci Rep 6:21769. https://doi.org/10.1038/srep21769
doi: 10.1038/srep21769
pubmed: 26878798
Fukata Y, Chen X, Chiken S et al (2021) LGI1–ADAM22–MAGUK configures transsynaptic nanoalignment for synaptic transmission and epilepsy prevention. Proc Natl Acad Sci USA 118:e2022580118. https://doi.org/10.1073/pnas.2022580118
doi: 10.1073/pnas.2022580118
pubmed: 33397806
Seagar M, Russier M, Caillard O et al (2017) LGI1 tunes intrinsic excitability by regulating the density of axonal Kv1 channels. Proc Natl Acad Sci USA 114:7719–7724. https://doi.org/10.1073/pnas.1618656114
doi: 10.1073/pnas.1618656114
pubmed: 28673977
Hivert B, Marien L, Agbam KN, Faivre-Sarrailh C (2019) ADAM22 and ADAM23 modulate the targeting of the Kv1 channel-associated protein LGI1 to the axon initial segment. J Cell Sci. https://doi.org/10.1242/jcs.219774
doi: 10.1242/jcs.219774
pubmed: 30598502
Ribeiro PAO, Sbragia L, Gilioli R et al (2008) Expression profile of Lgi1 gene in mouse brain during development. J Mol Neurosci 35:323–329. https://doi.org/10.1007/s12031-008-9096-0
doi: 10.1007/s12031-008-9096-0
pubmed: 18563303
Thomas R, Favell K, Morante-Redolat J et al (2010) LGI1 Is a nogo receptor 1 ligand that antagonizes myelin-based growth inhibition. J Neurosci 30:6607–6612. https://doi.org/10.1523/JNEUROSCI.5147-09.2010
doi: 10.1523/JNEUROSCI.5147-09.2010
pubmed: 20463223
Kusuzawa S, Honda T, Fukata Y et al (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: nuclear translocation of Lgi1. Eur J Neurosci 36:2284–2292. https://doi.org/10.1111/j.1460-9568.2012.08129.x
doi: 10.1111/j.1460-9568.2012.08129.x
pubmed: 22612501
Fukata Y, Lovero KL, Iwanaga T et al (2010) Disruption of LGI1–linked synaptic complex causes abnormal synaptic transmission and epilepsy. Proc Natl Acad Sci USA 107:3799–3804. https://doi.org/10.1073/pnas.0914537107
doi: 10.1073/pnas.0914537107
pubmed: 20133599
Gödde NJ, D’Abaco GM, Paradiso L, Novak U (2006) Efficient ADAM22 surface expression is mediated by phosphorylation-dependent interaction with 14–3-3 protein family members. J Cell Sci 119:3296–3305. https://doi.org/10.1242/jcs.03065
doi: 10.1242/jcs.03065
pubmed: 16868027
Yu YE, Wen L, Silva J et al (2010) Lgi1 null mutant mice exhibit myoclonic seizures and CA1 neuronal hyperexcitability. Hum Mol Genet 19:1702–1711. https://doi.org/10.1093/hmg/ddq047
doi: 10.1093/hmg/ddq047
pubmed: 20130004
Kole MJ, Qian J, Waase MP et al (2015) Selective loss of presynaptic potassium channel clusters at the cerebellar basket cell terminal pinceau in adam11 mutants reveals their role in ephaptic control of Purkinje cell firing. J Neurosci 35:11433–11444. https://doi.org/10.1523/JNEUROSCI.1346-15.2015
doi: 10.1523/JNEUROSCI.1346-15.2015
pubmed: 26269648
Sagane K, Hayakawa K, Kai J et al (2005) Ataxia and peripheral nerve hypomyelination in ADAM22-deficient mice. BMC Neurosci 6:33. https://doi.org/10.1186/1471-2202-6-33
doi: 10.1186/1471-2202-6-33
pubmed: 15876356
Owuor K, Harel NY, Englot DJ et al (2009) LGI1-associated epilepsy through altered ADAM23-dependent neuronal morphology. Mol Cell Neurosci 42:448–457. https://doi.org/10.1016/j.mcn.2009.09.008
doi: 10.1016/j.mcn.2009.09.008
pubmed: 19796686
Smart SL, Lopantsev V, Zhang CL et al (1998) Deletion of the KV1.1 potassium channel causes epilepsy in mice. Neuron 20:809–819. https://doi.org/10.1016/S0896-6273(00)81018-1
doi: 10.1016/S0896-6273(00)81018-1
pubmed: 9581771
Brew HM, Gittelman JX, Silverstein RS et al (2007) Seizures and reduced life span in mice lacking the potassium channel subunit Kv1.2, but hypoexcitability and enlarged Kv1 currents in auditory neurons. J Neurophysiol 98:1501–1525. https://doi.org/10.1152/jn.00640.2006
doi: 10.1152/jn.00640.2006
pubmed: 17634333
Edwards D, Handsley M, Pennington C (2008) The ADAM metalloproteinases. Mol Aspects Med 29:258–289. https://doi.org/10.1016/j.mam.2008.08.001
doi: 10.1016/j.mam.2008.08.001
pubmed: 18762209
Sagane K, Yamazaki K, Mizui Y, Tanaka I (1999) Cloning and chromosomal mapping of mouse ADAM11, ADAM22 and ADAM23. Gene 236:79–86. https://doi.org/10.1016/s0378-1119(99)00253-x
doi: 10.1016/s0378-1119(99)00253-x
pubmed: 10433968
Liu H, Shim AHR, He X (2009) Structural characterization of the ectodomain of a disintegrin and metalloproteinase-22 (ADAM22), a neural adhesion receptor instead of metalloproteinase. J Biol Chem 284:29077–29086. https://doi.org/10.1074/jbc.M109.014258
doi: 10.1074/jbc.M109.014258
pubmed: 19692335
El-Husseini AE, Schnell E, Chetkovich DM et al (2000) PSD-95 involvement in maturation of excitatory synapses. Science 290:1364–1368
doi: 10.1126/science.290.5495.1364
Yokoi N, Fukata Y, Kase D et al (2015) Chemical corrector treatment ameliorates increased seizure susceptibility in a mouse model of familial epilepsy. Nat Med 21:19–26. https://doi.org/10.1038/nm.3759
doi: 10.1038/nm.3759
pubmed: 25485908
Fournier AE, GrandPre T, Strittmatter SM (2001) Identification of a receptor mediating Nogo-66 inhibition of axonal regeneration. Nature 409:341–346. https://doi.org/10.1038/35053072
doi: 10.1038/35053072
pubmed: 11201742
Thomas RA, Gibon J, Chen CXQ et al (2018) The Nogo receptor ligand LGI1 regulates synapse number and synaptic activity in hippocampal and cortical neurons. eNeuro. https://doi.org/10.1523/ENEURO.0185-18.2018
doi: 10.1523/ENEURO.0185-18.2018
pubmed: 30225353
Schulte U, Thumfart J-O, Klöcker N et al (2006) The epilepsy-linked Lgi1 protein assembles into presynaptic Kv1 channels and inhibits inactivation by Kvbeta1. Neuron 49:697–706. https://doi.org/10.1016/j.neuron.2006.01.033
doi: 10.1016/j.neuron.2006.01.033
pubmed: 16504945
Savtchenko LP, Rusakov DA (2007) The optimal height of the synaptic cleft. Proc Natl Acad Sci U S A 104:1823–1828. https://doi.org/10.1073/pnas.0606636104
doi: 10.1073/pnas.0606636104
pubmed: 17261811
Silva J, Sharma S, Cowell JK (2015) Homozygous deletion of the LGI1 gene in mice leads to developmental abnormalities resulting in cortical dysplasia: loss of LGI1 leads to cortical dysplasia. Brain Pathol 25:587–597. https://doi.org/10.1111/bpa.12225
doi: 10.1111/bpa.12225
pubmed: 25346110
Silva J, Qin H, Cowell JK (2019) Selective inactivation of LGI1 in neuronal precursor cells leads to cortical dysplasia in mice. Genesis 57:e23268. https://doi.org/10.1002/dvg.23268
doi: 10.1002/dvg.23268
pubmed: 30489685
Xie Y-J, Zhou L, Jiang N et al (2015) Essential roles of leucine-rich glioma inactivated 1 in the development of embryonic and postnatal cerebellum. Sci Rep 5:7827. https://doi.org/10.1038/srep07827
doi: 10.1038/srep07827
pubmed: 25591666
Wills ZP, Mandel-Brehm C, Mardinly AR et al (2012) The Nogo receptor family restricts synapse number in the developing hippocampus. Neuron 73:466–481. https://doi.org/10.1016/j.neuron.2011.11.029
doi: 10.1016/j.neuron.2011.11.029
pubmed: 22325200
Luo L (2000) Rho GTPases in neuronal morphogenesis. Nat Rev Neurosci 1:173–180. https://doi.org/10.1038/35044547
doi: 10.1038/35044547
pubmed: 11257905
Silva J, Sharma S, Hughes B et al (2010) Homozygous inactivation of the LGI1 gene results in hypomyelination in the peripheral and central nervous systems: hypomyelination in LGI1 null mice. J Neurosci Res 88:3328–3336. https://doi.org/10.1002/jnr.22496
doi: 10.1002/jnr.22496
pubmed: 20857514
Lebrun-Julien F, Bachmann L, Norrmén C et al (2014) Balanced mTORC1 activity in oligodendrocytes is required for accurate CNS myelination. J Neurosci 34:8432–8448. https://doi.org/10.1523/JNEUROSCI.1105-14.2014
doi: 10.1523/JNEUROSCI.1105-14.2014
pubmed: 24948799
Ovsepian SV, LeBerre M, Steuber V et al (2016) Distinctive role of KV1.1 subunit in the biology and functions of low threshold K+ channels with implications for neurological disease. Pharmacol Ther 159:93–101. https://doi.org/10.1016/j.pharmthera.2016.01.005
doi: 10.1016/j.pharmthera.2016.01.005
pubmed: 26825872
Dodson PD, Forsythe ID (2004) Presynaptic K+ channels: electrifying regulators of synaptic terminal excitability. Trends Neurosci 27:210–217. https://doi.org/10.1016/j.tins.2004.02.012
doi: 10.1016/j.tins.2004.02.012
pubmed: 15046880
Trimmer JS (2015) Subcellular localization of K+ channels in mammalian brain neurons: remarkable precision in the midst of extraordinary complexity. Neuron 85:238–256. https://doi.org/10.1016/j.neuron.2014.12.042
doi: 10.1016/j.neuron.2014.12.042
pubmed: 25611506
Guan D, Lee JCF, Tkatch T et al (2006) Expression and biophysical properties of Kv1 channels in supragranular neocortical pyramidal neurones. J Physiol 571:371–389. https://doi.org/10.1113/jphysiol.2005.097006
doi: 10.1113/jphysiol.2005.097006
pubmed: 16373387
Guan D, Lee JCF, Higgs MH et al (2007) Functional roles of Kv1 channels in neocortical pyramidal neurons. J Neurophysiol 97:1931–1940. https://doi.org/10.1152/jn.00933.2006
doi: 10.1152/jn.00933.2006
pubmed: 17215507
Cudmore RH, Fronzaroli-Molinieres L, Giraud P, Debanne D (2010) Spike-time precision and network synchrony are controlled by the homeostatic regulation of the D-type potassium current. J Neurosci 30:12885–12895. https://doi.org/10.1523/JNEUROSCI.0740-10.2010
doi: 10.1523/JNEUROSCI.0740-10.2010
pubmed: 20861392
Yellen G (2002) The voltage-gated potassium channels and their relatives. Nature 419:35–42. https://doi.org/10.1038/nature00978
doi: 10.1038/nature00978
pubmed: 12214225
Ovsepian SV, Steuber V, Le Berre M et al (2013) A defined heteromeric K
doi: 10.1113/jphysiol.2012.249706
pubmed: 23318870
Guan D, Pathak D, Foehring RC (2018) Functional roles of Kv1-mediated currents in genetically identified subtypes of pyramidal neurons in layer 5 of mouse somatosensory cortex. J Neurophysiol 120:394–408. https://doi.org/10.1152/jn.00691.2017
doi: 10.1152/jn.00691.2017
pubmed: 29641306
Wang FC, Bell N, Reid P et al (1999) Identification of residues in dendrotoxin K responsible for its discrimination between neuronal K+ channels containing Kv1.1 and 1.2 alpha subunits. Eur J Biochem 263:222–229. https://doi.org/10.1046/j.1432-1327.1999.00494.x
doi: 10.1046/j.1432-1327.1999.00494.x
pubmed: 10429207
Harvey AL, Robertson B (2004) Dendrotoxins: structure-activity relationships and effects on potassium ion channels. CMC 11:3065–3072. https://doi.org/10.2174/0929867043363820
doi: 10.2174/0929867043363820
Zhou L, Zhou L, Su L et al (2018) Celecoxib ameliorates seizure susceptibility in autosomal dominant lateral temporal epilepsy. J Neurosci 38:3346–3357. https://doi.org/10.1523/JNEUROSCI.3245-17.2018
doi: 10.1523/JNEUROSCI.3245-17.2018
pubmed: 29491011
Lancaster E, Burnor E, Zhang J, Lancaster E (2019) ADAM23 is a negative regulator of Kv1.1/Kv1.4 potassium currents. Neurosci Lett 704:159–163. https://doi.org/10.1016/j.neulet.2019.04.012
doi: 10.1016/j.neulet.2019.04.012
pubmed: 30965109
Henley JM, Nair JD, Seager R et al (2021) Kainate and AMPA receptors in epilepsy: cell biology, signalling pathways and possible crosstalk. Neuropharmacology 195:108569. https://doi.org/10.1016/j.neuropharm.2021.108569
doi: 10.1016/j.neuropharm.2021.108569
pubmed: 33915142
Schnell E, Sizemore M, Karimzadegan S et al (2002) Direct interactions between PSD-95 and stargazin control synaptic AMPA receptor number. Proc Natl Acad Sci U S A 99:13902–13907. https://doi.org/10.1073/pnas.172511199
doi: 10.1073/pnas.172511199
pubmed: 12359873
von Ossowski L, Tossavainen H, von Ossowski I et al (2006) Peptide binding and NMR analysis of the interaction between SAP97 PDZ2 and GluR-A: potential involvement of a disulfide bond. Biochemistry 45:5567–5575. https://doi.org/10.1021/bi0511989
doi: 10.1021/bi0511989
Ottman R, Risch N, Hauser WA et al (1995) Localization of a gene for partial epilepsy to chromosome 10q. Nat Genet 10:56–60. https://doi.org/10.1038/ng0595-56
doi: 10.1038/ng0595-56
pubmed: 7647791
Dazzo E, Fanciulli M, Serioli E et al (2015) Heterozygous reelin mutations cause autosomal-dominant lateral temporal epilepsy. Am J Hum Genet 96:992–1000. https://doi.org/10.1016/j.ajhg.2015.04.020
doi: 10.1016/j.ajhg.2015.04.020
pubmed: 26046367
Michelucci R, Poza JJ, Sofia V et al (2003) Autosomal dominant lateral temporal epilepsy: clinical spectrum, new epitempin mutations, and genetic heterogeneity in seven European families: familial lateral temporal epilepsy. Epilepsia 44:1289–1297. https://doi.org/10.1046/j.1528-1157.2003.20003.x
doi: 10.1046/j.1528-1157.2003.20003.x
pubmed: 14510822
Michelucci R, Pasini E, Malacrida S et al (2013) Low penetrance of autosomal dominant lateral temporal epilepsy in Italian families without LGI1 mutations. Epilepsia 54:1288–1297. https://doi.org/10.1111/epi.12194
doi: 10.1111/epi.12194
pubmed: 23621105
Bisulli F, Naldi I, Baldassari S et al (2014) Autosomal dominant partial epilepsy with auditory features: a new locus on chromosome 19q13.11-q13.31. Epilepsia 55:841–848. https://doi.org/10.1111/epi.12560
doi: 10.1111/epi.12560
pubmed: 24579982
Boillot M, Baulac S (2016) Genetic models of focal epilepsies. J Neurosci Methods 260:132–143. https://doi.org/10.1016/j.jneumeth.2015.06.003
doi: 10.1016/j.jneumeth.2015.06.003
pubmed: 26072248
Yamagata A, Fukai S (2020) Insights into the mechanisms of epilepsy from structural biology of LGI1–ADAM22. Cell Mol Life Sci 77:267–274. https://doi.org/10.1007/s00018-019-03269-0
doi: 10.1007/s00018-019-03269-0
pubmed: 31432233
Baulac S, Ishida S, Mashimo T et al (2012) A rat model for LGI1-related epilepsies. Hum Mol Genet 21:3546–3557. https://doi.org/10.1093/hmg/dds184
doi: 10.1093/hmg/dds184
pubmed: 22589250
Striano P, Busolin G, Santulli L et al (2011) Familial temporal lobe epilepsy with psychic auras associated with a novel LGI1 mutation. Neurology 76:1173–1176. https://doi.org/10.1212/WNL.0b013e318212ab2e
doi: 10.1212/WNL.0b013e318212ab2e
pubmed: 21444903
Rosanoff MJ, Ottman R (2008) Penetrance of LGI1 mutations in autosomal dominant partial epilepsy with auditory features. Neurology 71:567–571. https://doi.org/10.1212/01.wnl.0000323926.77565.ee
doi: 10.1212/01.wnl.0000323926.77565.ee
pubmed: 18711109
Nobile C, Michelucci R, Andreazza S et al (2009) LGI1 mutations in autosomal dominant and sporadic lateral temporal epilepsy. Hum Mutat 30:530–536. https://doi.org/10.1002/humu.20925
doi: 10.1002/humu.20925
pubmed: 19191227
Vincent A, Buckley C, Schott JM et al (2004) Potassium channel antibody-associated encephalopathy: a potentially immunotherapy-responsive form of limbic encephalitis. Brain 127:701–712. https://doi.org/10.1093/brain/awh077
doi: 10.1093/brain/awh077
pubmed: 14960497
de Bruijn MAAM, van Sonderen A, van Coevorden-Hameete MH et al (2019) Evaluation of seizure treatment in anti-LGI1, anti-NMDAR, and anti-GABA
doi: 10.1212/WNL.0000000000007475
pubmed: 30979857
Shen C, Fang G, Yang F et al (2020) Seizures and risk of epilepsy in anti-NMDAR, anti-LGI1, and anti-GABABR encephalitis. Ann Clin Transl Neurol 7:1392–1399. https://doi.org/10.1002/acn3.51137
doi: 10.1002/acn3.51137
pubmed: 32710704
Ilyas-Feldmann M, Prüß H, Holtkamp M (2021) Long-term seizure outcome and antiseizure medication use in autoimmune encephalitis. Seizure 86:138–143. https://doi.org/10.1016/j.seizure.2021.02.010
doi: 10.1016/j.seizure.2021.02.010
pubmed: 33618141
Qiao S, Wu H-K, Liu L-L et al (2021) Characteristics and prognosis of autoimmune encephalitis in the East of China: a multi-center study. Front Neurol 12:642078. https://doi.org/10.3389/fneur.2021.642078
doi: 10.3389/fneur.2021.642078
pubmed: 34135845
Shan W, Yang H, Wang Q (2021) Neuronal surface antibody-medicated autoimmune encephalitis (limbic encephalitis) in China: a multiple-center retrospective study. Front Immunol 12:621599. https://doi.org/10.3389/fimmu.2021.621599
doi: 10.3389/fimmu.2021.621599
pubmed: 33679765
Cousyn L, Lambrecq V, Houot M et al (2021) Seizures in autoimmune encephalitis: specific features from a systematic comparative study. Epileptic Disord. https://doi.org/10.1684/epd.2021.1355
doi: 10.1684/epd.2021.1355
pubmed: 34704941
Qiao S, Wu H, Liu L et al (2021) Clinical features and long-term outcomes of anti-leucine-rich glioma-inactivated 1 encephalitis: a multi-center study. NDT 17:203–212. https://doi.org/10.2147/NDT.S292343
doi: 10.2147/NDT.S292343
Lin N, Liu Q, Chen J et al (2021) Long-term seizure outcomes in patients with anti-leucine-rich glioma-inactivated 1 encephalitis. Epilepsy Behav 122:108159. https://doi.org/10.1016/j.yebeh.2021.108159
doi: 10.1016/j.yebeh.2021.108159
pubmed: 34229158
Li T-R, Zhang Y-D, Wang Q et al (2021) Clinical characteristics and long-term prognosis of anti-LGI1 encephalitis: a single-center cohort study in Beijing. China Front Neurol 12:674368. https://doi.org/10.3389/fneur.2021.674368
doi: 10.3389/fneur.2021.674368
pubmed: 34168612
Zhao Q, Sun L, Zhao D et al (2021) Clinical features of anti-leucine-rich glioma-inactivated 1 encephalitis in northeast China. Clin Neurol Neurosurg 203:106542. https://doi.org/10.1016/j.clineuro.2021.106542
doi: 10.1016/j.clineuro.2021.106542
pubmed: 33706063
van Sonderen A, Schreurs MWJ, de Bruijn MAAM et al (2016) The relevance of VGKC positivity in the absence of LGI1 and Caspr2 antibodies. Neurology 86:1692–1699. https://doi.org/10.1212/WNL.0000000000002637
doi: 10.1212/WNL.0000000000002637
pubmed: 27037230
Binks SNM, Veldsman M, Easton A et al (2021) Residual fatigue and cognitive deficits in patients after leucine-rich glioma-inactivated 1 antibody encephalitis. JAMA Neurol 78:617. https://doi.org/10.1001/jamaneurol.2021.0477
doi: 10.1001/jamaneurol.2021.0477
pubmed: 33779685
Kim T-J, Lee S-T, Moon J et al (2017) Anti-LGI1 encephalitis is associated with unique HLA subtypes: HLA subtypes in anti-LGI1 encephalitis. Ann Neurol 81:183–192. https://doi.org/10.1002/ana.24860
doi: 10.1002/ana.24860
pubmed: 28026029
van Sonderen A, Roelen DL, Stoop JA et al (2017) Anti-LGI1 encephalitis is strongly associated with HLA-DR7 and HLA-DRB4: anti-LGI1 encephalitis. Ann Neurol 81:193–198. https://doi.org/10.1002/ana.24858
doi: 10.1002/ana.24858
pubmed: 28026046
Binks S, Varley J, Lee W et al (2018) Distinct HLA associations of LGI1 and CASPR2-antibody diseases. Brain 141:2263–2271. https://doi.org/10.1093/brain/awy109
doi: 10.1093/brain/awy109
pubmed: 29788256
Muñiz-Castrillo S, Haesebaert J, Thomas L et al (2021) Clinical and prognostic value of immunogenetic characteristics in anti-LGI1 encephalitis. Neurol Neuroimmunol Neuroinflamm 8:e974. https://doi.org/10.1212/NXI.0000000000000974
doi: 10.1212/NXI.0000000000000974
pubmed: 33848259
Wennberg R, Steriade C, Chen R, Andrade D (2018) Frontal infraslow activity marks the motor spasms of anti-LGI1 encephalitis. Clin Neurophysiol 129:59–68. https://doi.org/10.1016/j.clinph.2017.10.014
doi: 10.1016/j.clinph.2017.10.014
pubmed: 29145168
Liu X, Han Y, Yang L et al (2020) The exploration of the spectrum of motor manifestations of anti-LGI1 encephalitis beyond FBDS. Seizure 76:22–27. https://doi.org/10.1016/j.seizure.2019.12.023
doi: 10.1016/j.seizure.2019.12.023
pubmed: 31972532
Flanagan EP, Kotsenas AL, Britton JW et al (2015) Basal ganglia T1 hyperintensity in LGI1-autoantibody faciobrachial dystonic seizures. Neurol Neuroimmunol Neuroinflamm 2:e161. https://doi.org/10.1212/NXI.0000000000000161
doi: 10.1212/NXI.0000000000000161
pubmed: 26468474
Liu X, Shan W, Zhao X et al (2020) The clinical value of 18F-FDG-PET in autoimmune encephalitis associated with LGI1 antibody. Front Neurol 11:418. https://doi.org/10.3389/fneur.2020.00418
doi: 10.3389/fneur.2020.00418
pubmed: 32581996
Brüggemann N (2021) Contemporary functional neuroanatomy and pathophysiology of dystonia. J Neural Transm (Vienna) 128:499–508. https://doi.org/10.1007/s00702-021-02299-y
doi: 10.1007/s00702-021-02299-y
Celicanin M, Blaabjerg M, Maersk-Moller C et al (2017) Autoimmune encephalitis associated with voltage-gated potassium channels-complex and leucine-rich glioma-inactivated 1 antibodies - a national cohort study. Eur J Neurol 24:999–1005. https://doi.org/10.1111/ene.13324
doi: 10.1111/ene.13324
pubmed: 28544133
Hang H, Zhang J, Chen D et al (2020) Clinical characteristics of cognitive impairment and 1-year outcome in patients with anti-LGI1 antibody encephalitis. Front Neurol 11:852. https://doi.org/10.3389/fneur.2020.00852
doi: 10.3389/fneur.2020.00852
pubmed: 33162923
Ramanathan S, Tseng M, Davies AJ et al (2021) LGI1- versus CASPR2-antibody neuropathic pain: clinical and biological comparisons. Ann Neurol. https://doi.org/10.1002/ana.26189
doi: 10.1002/ana.26189
pubmed: 34862658
van Sonderen A, Thijs RD, Coenders EC et al (2016) Anti-LGI1 encephalitis: clinical syndrome and long-term follow-up. Neurology 87:1449–1456. https://doi.org/10.1212/WNL.0000000000003173
doi: 10.1212/WNL.0000000000003173
pubmed: 27590293
Chen W, Wang M, Gao L et al (2021) Neurofunctional outcomes in patients with anti-leucine-rich glioma inactivated 1 encephalitis. Acta Neurol Scand. https://doi.org/10.1111/ane.13503
doi: 10.1111/ane.13503
pubmed: 34779509
Smith KM, Dubey D, Liebo GB et al (2021) Clinical course and features of seizures associated with LGI1-antibody encephalitis. Neurology. https://doi.org/10.1212/WNL.0000000000012465
doi: 10.1212/WNL.0000000000012465
pubmed: 34992956
Ariño H, Armangué T, Petit-Pedrol M et al (2016) Anti-LGI1–associated cognitive impairment: presentation and long-term outcome. Neurology 87:759–765. https://doi.org/10.1212/WNL.0000000000003009
doi: 10.1212/WNL.0000000000003009
pubmed: 27466467
Thompson J, Bi M, Murchison AG et al (2018) The importance of early immunotherapy in patients with faciobrachial dystonic seizures. Brain 141:348–356. https://doi.org/10.1093/brain/awx323
doi: 10.1093/brain/awx323
pubmed: 29272336
Bien CG, Bien CI, Dogan Onugoren M et al (2020) Routine diagnostics for neural antibodies, clinical correlates, treatment and functional outcome. J Neurol 267:2101–2114. https://doi.org/10.1007/s00415-020-09814-3
doi: 10.1007/s00415-020-09814-3
pubmed: 32246252
Koneczny I (2018) A new classification system for IgG4 autoantibodies. Front Immunol 9:97. https://doi.org/10.3389/fimmu.2018.00097
doi: 10.3389/fimmu.2018.00097
pubmed: 29483905
Ramberger M, Berretta A, Tan JMM et al (2020) Distinctive binding properties of human monoclonal LGI1 autoantibodies determine pathogenic mechanisms. Brain 143:1731–1745. https://doi.org/10.1093/brain/awaa104
doi: 10.1093/brain/awaa104
pubmed: 32437528
González-Burgos I, Velázquez-Zamora DA, Beas-Zárate C (2009) Damage and plasticity in adult rat hippocampal trisynaptic circuit neurons after neonatal exposure to glutamate excitotoxicity. Int J Dev Neurosci 27:741–745. https://doi.org/10.1016/j.ijdevneu.2009.08.016
doi: 10.1016/j.ijdevneu.2009.08.016
pubmed: 19733648
Irani SR, Stagg CJ, Schott JM et al (2013) Faciobrachial dystonic seizures: the influence of immunotherapy on seizure control and prevention of cognitive impairment in a broadening phenotype. Brain 136:3151–3162. https://doi.org/10.1093/brain/awt212
doi: 10.1093/brain/awt212
pubmed: 24014519
Feyissa AM, Lamb C, Pittock SJ et al (2018) Antiepileptic drug therapy in autoimmune epilepsy associated with antibodies targeting the leucine-rich glioma-inactivated protein 1. Epilepsia Open 3:348–356. https://doi.org/10.1002/epi4.12226
doi: 10.1002/epi4.12226
pubmed: 30187005
Dubey D, Britton J, McKeon A et al (2020) Randomized placebo-controlled trial of intravenous immunoglobulin in autoimmune LGI1/CASPR2 epilepsy. Ann Neurol 87:313–323. https://doi.org/10.1002/ana.25655
doi: 10.1002/ana.25655
pubmed: 31782181
Petit-Pedrol M, Sell J, Planagumà J et al (2018) LGI1 antibodies alter Kv1.1 and AMPA receptors changing synaptic excitability, plasticity and memory. Brain. https://doi.org/10.1093/brain/awy253
doi: 10.1093/brain/awy253
pubmed: 30346486
Zhang T-Y, Cai M-T, Zheng Y et al (2021) Anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor encephalitis: a review. Front Immunol 12:652820. https://doi.org/10.3389/fimmu.2021.652820
doi: 10.3389/fimmu.2021.652820
pubmed: 34093540