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Fels E, Muñiz-Castrillo S, Vogrig A, et al. Role of LGI1 protein in synaptic transmission: From physiology to pathology. Neurobiol Dis. 2021;160:105537doi: 10.1016/j.nbd.2021.105537.
Fels, E., Muñiz-Castrillo, S., Vogrig, A., Joubert, B., Honnorat, J., & Pascual, O. (2021). Role of LGI1 protein in synaptic transmission: From physiology to pathology. Neurobiology of disease, 160105537. https://doi.org/10.1016/j.nbd.2021.105537
Fels, Elodie, et al. "Role of LGI1 protein in synaptic transmission: From physiology to pathology." Neurobiology of disease vol. 160 (2021): 105537. doi: https://doi.org/10.1016/j.nbd.2021.105537
Fels E, Muñiz-Castrillo S, Vogrig A, Joubert B, Honnorat J, Pascual O. Role of LGI1 protein in synaptic transmission: From physiology to pathology. Neurobiol Dis. 2021 Dec;160:105537. doi: 10.1016/j.nbd.2021.105537. Epub 2021 Oct 22. PMID: 34695575.
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Neurobiol Dis. 2021 Dec;160:105537. doi: 10.1016/j.nbd.2021.105537. Epub 2021 Oct 22.

Role of LGI1 protein in synaptic transmission: From physiology to pathology.

Neurobiology of disease

Elodie Fels, Sergio Muñiz-Castrillo, Alberto Vogrig, Bastien Joubert, Jérôme Honnorat, Olivier Pascual

Affiliations

  1. Synaptopathies and Auto-antibodies (SynatAc) Team, Institut NeuroMyoGène, INSERM U1217/CNRS UMR 5310, Universités de Lyon, Université Claude Bernard Lyon 1, Lyon, France; Université Claude Bernard Lyon 1, Universités de Lyon, Lyon, France.
  2. Synaptopathies and Auto-antibodies (SynatAc) Team, Institut NeuroMyoGène, INSERM U1217/CNRS UMR 5310, Universités de Lyon, Université Claude Bernard Lyon 1, Lyon, France; Université Claude Bernard Lyon 1, Universités de Lyon, Lyon, France; French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Hôpital Neurologique, 59 Boulevard Pinel, 69677 Bron Cedex, France.
  3. Université Claude Bernard Lyon 1, Universités de Lyon, Lyon, France; French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Hôpital Neurologique, 59 Boulevard Pinel, 69677 Bron Cedex, France.
  4. Synaptopathies and Auto-antibodies (SynatAc) Team, Institut NeuroMyoGène, INSERM U1217/CNRS UMR 5310, Universités de Lyon, Université Claude Bernard Lyon 1, Lyon, France; Université Claude Bernard Lyon 1, Universités de Lyon, Lyon, France; French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Hôpital Neurologique, 59 Boulevard Pinel, 69677 Bron Cedex, France. Electronic address: [email protected].
  5. Synaptopathies and Auto-antibodies (SynatAc) Team, Institut NeuroMyoGène, INSERM U1217/CNRS UMR 5310, Universités de Lyon, Université Claude Bernard Lyon 1, Lyon, France; Université Claude Bernard Lyon 1, Universités de Lyon, Lyon, France. Electronic address: [email protected].

PMID: 34695575 DOI: 10.1016/j.nbd.2021.105537

Abstract

Leucine-Rich Glioma Inactivated protein 1 (LGI1) is a secreted neuronal protein highly expressed in the central nervous system and high amount are found in the hippocampus. An alteration of its function has been described in few families of patients with autosomal dominant temporal lobe epilepsy (ADLTE) or with autoimmune limbic encephalitis (LE), both characterized by epileptic seizures. Studies have shown that LGI1 plays an essential role during development, but also in neuronal excitability through an action on voltage-gated potassium Kv1.1 channels, and in synaptic transmission by regulating the surface expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPA-R). Over the last decade, a growing number of studies investigating LGI1 functions have been published. They aimed to improve the understanding of LGI1 function in the regulation of neuronal networks using different animal and cellular models. LGI1 appears to be a major actor of synaptic regulation by modulating trans-synaptically pre- and post-synaptic proteins. In this review, we will focus on LGI1 binding partners, "A Disintegrin And Metalloprotease (ADAM) 22 and 23", the complex they form at the synapse, and will discuss the effects of LGI1 on neuronal excitability and synaptic transmission in physiological and pathological conditions. Finally, we will highlight new insights regarding N-terminal Leucine-Rich Repeat (LRR) domain and C-terminal Epitempin repeat (EPTP) domain and their potentially distinct role in LGI1 function.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Keywords: Autoimmune limbic encephalitis; Autosomal dominant temporal lobe epilepsy; Synaptic transmission; Trans-synaptic complex

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