Disruption of LGI1-linked synaptic complex causes abnormal synaptic transmission and epilepsy

Y. Fukata, K. Lovero, T. Iwanaga, A. Watanabe, N. Yokoi, K. Tabuchi, R. Shigemoto, R. Nicoll, M. Fukata, PNAS 107 (2010) 3799–3804.

Download
No fulltext has been uploaded. References only!

Journal Article | Published
Author
; ; ; ; ; ; ; ;
Abstract
Epilepsy is a devastating and poorly understood disease. Mutations in a secreted neuronal protein, leucine-rich glioma inactivated 1 (LGI1), were reported in patients with an inherited form of human epilepsy, autosomal dominant partial epilepsy with auditory features (ADPEAF). Here, we report an essential role of LGI1 as an antiepileptogenic ligand. We find that loss of LGI1 in mice (LGI1-/-) causes lethal epilepsy, which is specifically rescued by the neuronal expression of LGI1 transgene, but not LGI3. Moreover, heterozygous mice for the LGI1 mutation (LGI1+/-) show lowered seizure thresholds. Extracellularly secreted LGI1 links two epilepsy-related receptors, ADAM22 and ADAM23, in the brain and organizes a transsynaptic protein complex that includes presynaptic potassium channels and postsynaptic AMPA receptor scaffolds. A lack of LGI1 disrupts this synaptic protein connection and selectively reduces AMPA receptor-mediated synaptic transmission in the hippocampus. Thus, LGI1 may serve as a major determinant of brain excitation, and the LGI1 gene-targeted mouse provides a good model for human epilepsy.
Publishing Year
Date Published
2010-02-23
Journal Title
PNAS
Volume
107
Issue
8
Page
3799 - 3804
IST-REx-ID

Cite this

Fukata Y, Lovero K, Iwanaga T, et al. Disruption of LGI1-linked synaptic complex causes abnormal synaptic transmission and epilepsy. PNAS. 2010;107(8):3799-3804. doi:10.1073/pnas.0914537107
Fukata, Y., Lovero, K., Iwanaga, T., Watanabe, A., Yokoi, N., Tabuchi, K., … Fukata, M. (2010). Disruption of LGI1-linked synaptic complex causes abnormal synaptic transmission and epilepsy. PNAS, 107(8), 3799–3804. https://doi.org/10.1073/pnas.0914537107
Fukata, Yuko, Kathryn Lovero, Tsuyoshi Iwanaga, Atsushi Watanabe, Norihiko Yokoi, Katsuhiko Tabuchi, Ryuichi Shigemoto, Roger Nicoll, and Masaki Fukata. “Disruption of LGI1-Linked Synaptic Complex Causes Abnormal Synaptic Transmission and Epilepsy.” PNAS 107, no. 8 (2010): 3799–3804. https://doi.org/10.1073/pnas.0914537107.
Y. Fukata et al., “Disruption of LGI1-linked synaptic complex causes abnormal synaptic transmission and epilepsy,” PNAS, vol. 107, no. 8, pp. 3799–3804, 2010.
Fukata Y, Lovero K, Iwanaga T, Watanabe A, Yokoi N, Tabuchi K, Shigemoto R, Nicoll R, Fukata M. 2010. Disruption of LGI1-linked synaptic complex causes abnormal synaptic transmission and epilepsy. PNAS. 107(8), 3799–3804.
Fukata, Yuko, et al. “Disruption of LGI1-Linked Synaptic Complex Causes Abnormal Synaptic Transmission and Epilepsy.” PNAS, vol. 107, no. 8, National Academy of Sciences, 2010, pp. 3799–804, doi:10.1073/pnas.0914537107.

Export

Marked Publications

Open Data IST Research Explorer

Search this title in

Google Scholar