title: LGI1 is a Nogo receptor 1 ligand that antagonizes myelin-based growth inhibition.
abstract: Mutations in leucine-rich glioma inactivated (LGI1) are a genetic cause of autosomal dominant temporal lobe epilepsy with auditory features. LGI1 is a secreted protein that shares homology with members of the SLIT family, ligands that direct axonal repulsion and growth cone collapse, and we therefore considered the possibility that LGI1 may regulate neuronal process extension or growth cone collapse. Here we report that LGI1 does not affect growth directly but instead enhances neuronal growth on myelin-based inhibitory substrates and antagonizes myelin-induced growth cone collapse. We show that LGI1 mediates this effect by functioning as a specific Nogo receptor 1 (NgR1) ligand that antagonizes the action of myelin-based inhibitory cues. Finally, we demonstrate that NgR1 and ADAM22 physically associate to form a receptor complex in which NgR1 facilitates LGI1 binding to ADAM22.
authors.affiliation: Centre for Neuronal Survival, Montreal Neurological Institute, McGill University, Montréal, Quebec H3A 2B4, Canada.
authors.forename: Rhalena
authors.initials: R
authors.lastname: Thomas
authors.forename: Kristy
authors.initials: K
authors.lastname: Favell
authors.forename: Jose
authors.initials: J
authors.lastname: Morante-Redolat
authors.forename: Madeline
authors.initials: M
authors.lastname: Pool
authors.forename: Christopher
authors.initials: C
authors.lastname: Kent
authors.forename: Melissa
authors.initials: M
authors.lastname: Wright
authors.forename: Kathleen
authors.initials: K
authors.lastname: Daignault
authors.forename: Gino B
authors.initials: GB
authors.lastname: Ferraro
authors.forename: Samuel
authors.initials: S
authors.lastname: Montcalm
authors.forename: Yves
authors.initials: Y
authors.lastname: Durocher
authors.forename: Alyson
authors.initials: A
authors.lastname: Fournier
authors.forename: Jordi
authors.initials: J
authors.lastname: Perez-Tur
authors.forename: Philip A
authors.initials: PA
authors.lastname: Barker
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000254:growth & development / Q000502:physiology; D019556:COS Cells; D049108:Cell Enlargement; D002460:Cell Line; D002642:Chick Embryo; D002522:Chlorocebus aethiops; D058851:GPI-Linked Proteins; D005727:Ganglia, Spinal / Q000254:growth & development / Q000502:physiology; D020439:Growth Cones / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009185:Myelin Proteins / Q000378:metabolism*; D009186:Myelin Sheath / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000378:metabolism*
chemical_list: D058851:GPI-Linked Proteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; C116499:LGI1 protein, human; C513865:Lgi1 protein, rat; D009185:Myelin Proteins; D009419:Nerve Tissue Proteins; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D011506:Proteins; C000603199:RTN4 protein, human; C486580:RTN4R protein, human; D011956:Receptors, Cell Surface; C000603197:Rtn4 protein, rat; C486581:Rtn4r protein, rat; C513864:Adam22 protein, rat; D051722:ADAM Proteins; C498474:ADAM22 protein, human
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