The epilepsy-linked Lgi1 protein assembles into presynaptic Kv1 channels and inhibits inactivation by Kvbeta1

Neuron
Uwe SchulteBernd Fakler

Abstract

The voltage-gated potassium (Kv) channel subunit Kv1.1 is a major constituent of presynaptic A-type channels that modulate synaptic transmission in CNS neurons. Here, we show that Kv1.1-containing channels are complexed with Lgi1, the functionally unassigned product of the leucine-rich glioma inactivated gene 1 (LGI1), which is causative for an autosomal dominant form of lateral temporal lobe epilepsy (ADLTE). In the hippocampal formation, both Kv1.1 and Lgi1 are coassembled with Kv1.4 and Kvbeta1 in axonal terminals. In A-type channels composed of these subunits, Lgi1 selectively prevents N-type inactivation mediated by the Kvbeta1 subunit. In contrast, defective Lgi1 molecules identified in ADLTE patients fail to exert this effect resulting in channels with rapid inactivation kinetics. The results establish Lgi1 as a novel subunit of Kv1.1-associated protein complexes and suggest that changes in inactivation gating of presynaptic A-type channels may promote epileptic activity.

References

Jan 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·M B JacksonG J Augustine
Jun 1, 1995·Current Opinion in Structural Biology·B Kobe, J Deisenhofer
Jul 22, 1999·Annals of the New York Academy of Sciences·W A CoetzeeB Rudy
Jan 26, 2002·Nature Genetics·Sergey KalachikovT Conrad Gilliam
Apr 30, 2002·Human Molecular Genetics·José M Morante-RedolatAdolfo López de Munain
Mar 4, 2003·Nature Neuroscience·Paco S HersonJames Maylie
Jun 14, 2003·The Neurologist·Melodie R Winawer
Nov 19, 2003·Archives of Neurology·Eliane KobayashiFernando Cendes
Dec 4, 2003·Epilepsy Research·Eylert BrodtkorbOrtrud K Steinlein
Feb 24, 2004·Annual Review of Physiology·James S Trimmer, Kenneth J Rhodes
Mar 30, 2004·Trends in Neurosciences·Paul D Dodson, Ian D Forsythe
Apr 22, 2004·Nature Reviews. Neuroscience·Ortrud K Steinlein
Jan 7, 2005·Nature·Jens S AndersenMatthias Mann
Apr 14, 2005·Neurogenetics·W GuO K Steinlein

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Citations

Nov 1, 2011·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Kari J EkenstedtJames R Mickelson
Sep 17, 2009·Histochemistry and Cell Biology·Manuela MalatestaCarlo Nobile
Mar 28, 2007·Cellular and Molecular Neurobiology·Nobuyuki KimuraYasuhiro Yoshikawa
Sep 6, 2007·Cellular and Molecular Neurobiology·Sachi Okabayashi, Nobuyuki Kimura
May 24, 2012·Current Neurology and Neuroscience Reports·Roberto MichelucciCarlo Nobile
Jun 20, 2008·Journal of Molecular Neuroscience : MN·Patrícia A O RibeiroIscia Lopes-Cendes
Feb 5, 2009·Journal of Molecular Neuroscience : MN·Fábio F ConteIscia Lopes-Cendes
Apr 24, 2009·Journal of Molecular Neuroscience : MN·Padmaja KunapuliJohn K Cowell
Jan 3, 2007·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Brian S Meldrum, Michael A Rogawski
Mar 31, 2007·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Sarah E HeronJohn C Mulley
Mar 31, 2007·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Sanjeev RajakulendranMichael G Hanna
Oct 9, 2009·Nature Medicine·Matteo Caleo
Dec 2, 2009·Nature Reviews. Drug Discovery·Heike WulffLuis A Pardo
Jan 26, 2011·Nature Reviews. Neurology·Angelo LabateFrederick Andermann
Aug 7, 2008·Proceedings of the National Academy of Sciences of the United States of America·Adam B WeinglassMaria L Garcia
Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Yuko FukataMasaki Fukata
Jul 30, 2010·Proceedings of the National Academy of Sciences of the United States of America·Catrin Swantje MüllerUwe Schulte
Mar 26, 2011·Proceedings of the National Academy of Sciences of the United States of America·Yaping PanMing Zhou
Oct 2, 2013·Proceedings of the National Academy of Sciences of the United States of America·Nirakar SahooStefan H Heinemann
Nov 10, 2011·Molecular & Cellular Proteomics : MCP·Wolfgang BildlUwe Schulte
Jun 25, 2008·Molecular & Cellular Proteomics : MCP·Jiusheng YanJames S Trimmer
Jul 28, 2010·Brain : a Journal of Neurology·Elodie ChabrolStéphanie Baulac
Feb 5, 2010·Human Molecular Genetics·Y Eugene YuJohn K Cowell
May 30, 2009·Epilepsia·Roberto MichelucciCarlo Nobile
Jan 30, 2007·Epilepsy Currents·Gregory C Mathews
Aug 19, 2007·Epilepsy Currents·Nicholas P Poolos
Dec 16, 2010·Epilepsy Currents·Matthew P Anderson
Mar 3, 2007·Genes, Brain, and Behavior·L M DibbensP Poronnik
Jun 15, 2007·Genes, Brain, and Behavior·L M DibbensJ C Mulley
Jul 13, 2011·Genes, Brain, and Behavior·J L WagnonW N Frankel
Oct 17, 2008·Physiological Reviews·Helene VacherJames S Trimmer
Jan 30, 2010·International Journal of Cell Biology·Nadia Gabellini, Valentina Masola
Oct 15, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Aaron J NorrisJeanne M Nerbonne
Nov 15, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Toshika OhkawaMasaki Fukata
Jan 22, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Yasuhiro OgawaMatthew N Rasband
Jan 21, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Yu-Dong ZhouMatthew P Anderson
Mar 12, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ekim OzkaynakDies Meijer
Nov 1, 2008·International Journal of Biological Sciences·Koji SaganeHachiro Sugimoto
Dec 11, 2013·Translational Stroke Research·Niyathi Hegde Shah, Elias Aizenman
Mar 26, 2014·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Renzo GuerriniMassimo Mantegazza

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