LGI1 is a Nogo Receptor 1 Ligand That Antagonizes Myelin-based Growth Inhibition

Overview

Journal J Neurosci

Specialty Neurology

Date 2010 May 14

PMID 20463223

Citations 48

Authors

Rhalena Thomas

Kristy Favell

Jose Morante-Redolat

Madeline Pool

Christopher Kent

Melissa Wright

Kathleen Daignault

Gino B Ferraro

Samuel Montcalm

Yves Durocher

Alyson Fournier

Jordi Perez-Tur

Philip A Barker

Affiliations

Soon will be listed here.

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.

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