Skip to main content
Log in

Distribution of the epilepsy-related Lgi1 protein in rat cortical neurons

  • Original Paper
  • Published:
Histochemistry and Cell Biology Aims and scope Submit manuscript

Abstract

The Lgi1 protein is involved in the pathogenesis of autosomal dominant lateral temporal epilepsy because mutations in the leucine-rich, glioma-inactivated 1 (LGI1) gene have been found in affected subjects and families; however, the function of Lgi1 is still unclear. Definition of the fine intracellular distribution of Lgi1 in normal cortical tissue would add in understanding its role and envisage pathogenetic mechanisms. Therefore, we analyzed normal rat cortex for Lgi1 by combining biochemistry, immunohistochemistry and immunoelectron microscopy. Our results demonstrate that Lgi1 is a cytoplasmic protein distributed both in the soma and in the processes of neurons: it occurs on the rough endoplasmic reticulum, the site of synthesis, in the Golgi complex, where it undergoes glycosylation, and in close proximity to neurotubules and neurofilaments, especially in the axons, but it is scarce at synapses and the neurilemma. Lgi1 association with axonal cytoskeletal structures would imply Lgi1 is either transported along axons by motor proteins, or playing some role as a carrier in the axonal flux, or it could be involved in the regulation of cytoskeletal organization.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Bendayan M, Zollinger M (1983) Ultrastructural localization of antigenic sites on osmium-fixed tissues applying the protein A-gold technique. J Histochem Cytochem 31:101–109

    CAS  PubMed  Google Scholar 

  • Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  CAS  PubMed  Google Scholar 

  • Brodtkorb E, Gu W, Nakken KO, Fischer C, Steinlein OK (2002) Familial temporal lobe epilepsy with aphasic seizures and linkage to chromosome 10q22–q24. Epilepsia 43:228–235

    Article  CAS  PubMed  Google Scholar 

  • Buchanan S, Gay NJ (1996) Structural and functional diversity in the leucine-rich repeat family of proteins. Prog Biophys Mol Biol 65:1–44

    Article  CAS  PubMed  Google Scholar 

  • Chabrol E, Popescu C, Gourfinkel-An I, Trouillard O, Depienne C, Senechal K, Baulac M, Le Guern E, Baulac S (2007) Two novel epilepsy-linked mutations leading to a loss of function of LGI1. Arch Neurol 64:217–222

    Article  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Cowell JK (2002) Epilepsy research gets new guidance. Nat Med 8:219–220

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Furlan S, Roncaroli F, Forner F, Vitiello L, Calabria E, Piquer-Sirerol S, Valle G, Perez-Tur J, Michelucci R, Nobile C (2006) The LGI1/epitempin gene encodes two protein isoforms differentially expressed in human brain. J Neurochem 98:985–991

    Article  CAS  PubMed  Google Scholar 

  • Gu W, Wevers A, Schroeder H, Grzeschik KH, Derst C, Brodtkorb E, de Vos R, Steinlein OK (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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • Kobe B, Kajava AV (2001) The leucine-rich repeat as a protein recognition motif. Curr Opin Struct Biol 11:725–732

    Article  CAS  PubMed  Google Scholar 

  • Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685

    Article  CAS  PubMed  Google Scholar 

  • Michelucci R, Poza JJ, Sofia V, de Feo MR, Binelli S, Bisulli F, Scudellaro E, Simionati B, Zimbello R, D’Orsi G, Passarelli D, Avoni P, Avanzini G, Tinuper P, Biondi R, Valle G, Mautner VF, Stephani U, Tassinari CA, Moschonas NK, Siebert R, Lopez de Munain A, Perez-Tur J, Nobile C (2003) Autosomal dominant lateral temporal epilepsy: clinical spectrum, new epitempin mutations, and genetic heterogeneity in seven European families. Epilepsia 44:1289–1297

    Article  CAS  PubMed  Google Scholar 

  • Morante-Redolat JM, Gorostidi-Pagola A, Piquer-Sirerol S, Saenz A, Poza JJ, Galan 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, Marti-Masso JF, Kluwe L, Deloukas P, Moschonas NK, Michelucci R, Siebert R, Nobile C, Perez-Tur J, Lopez de Munain A (2002) Mutations in the LGI1/epitempin gene on 10q24 cause autosomal dominant lateral temporal epilepsy. Hum Mol Genet 11:1119–1128

    Article  CAS  PubMed  Google Scholar 

  • Nobile C, Michelucci R, Andreazza S, Pasini E, Tosatto SCE, Striano P (2009) LGI1 mutations in autosomal dominant and sporadic lateral temporal epilepsy. Hum Mutat 30:530–536

    Article  CAS  PubMed  Google Scholar 

  • Ottman R, Risch N, Hauser WA, Pedley TA, Lee JH, Barker-Cummings C, Lustenberger A, Nagle KJ, Lee KS, Scheuer ML, Neystat M, Susser M, Wilhelmsen KC (1995) Localization of a gene for partial epilepsy to chromosome 10q. Nat Genet 10:56–60

    Article  CAS  PubMed  Google Scholar 

  • Ottman R, Winawer MR, Kalachikov S, Barker-Cummings C, Gilliam TC, Pedley TA, Hauser WA (2004) LGI1 mutations in autosomal dominant partial epilepsy with auditory features. Neurology 62:1120–1126

    CAS  PubMed  Google Scholar 

  • Paoli M (2001) Protein folds propelled by diversity. Prog Biophys Mol Biol 76:103–130

    Article  CAS  PubMed  Google Scholar 

  • 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 OK, 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

    Article  CAS  PubMed  Google Scholar 

  • Poza JJ, 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

    Article  CAS  PubMed  Google Scholar 

  • Ribeiro PA, 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Shelanski ML, Gaskin F, Cantor CR (1973) Microtubule assembly in the absence of added nucleotides. Proc Natl Acad Sci USA 70:765–768

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Striano P, de Falco A, Diani E, Bovo G, Furlan S, Vitiello L, Pinardi F, Striano S, Michelucci R, de Falco AF, Nobile C (2008) A novel loss-of-function LGI1 mutation linked to autosomal dominant lateral temporal epilepsy. Arch Neurol 65:939–942

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We are grateful to Dr. E. Lorenzetto for skillful technical assistance at confocal microscope. Part of this work was supported by the Genetic Commission of the Italian League against Epilepsy.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Manuela Malatesta.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Malatesta, M., Furlan, S., Mariotti, R. et al. Distribution of the epilepsy-related Lgi1 protein in rat cortical neurons. Histochem Cell Biol 132, 505–513 (2009). https://doi.org/10.1007/s00418-009-0637-6

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00418-009-0637-6

Keywords

Navigation