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Science 313 (5794): 1792-1795

Copyright © 2006 by the American Association for the Advancement of Science

Epilepsy-Related Ligand/Receptor Complex LGI1 and ADAM22 Regulate Synaptic Transmission

Yuko Fukata,1 Hillel Adesnik,2 Tsuyoshi Iwanaga,1 David S. Bredt,3 Roger A. Nicoll,2 Masaki Fukata1,4*

Abstract: Abnormally synchronized synaptic transmission in the brain causes epilepsy. Most inherited forms of epilepsy result from mutations in ion channels. However, one form of epilepsy, autosomal dominant partial epilepsy with auditory features (ADPEAF), is characterized by mutations in a secreted neuronal protein, LGI1. We show that ADAM22, a transmembrane protein that when mutated itself causes seizure, serves as a receptor for LGI1. LGI1 enhances AMPA receptor-mediated synaptic transmission in hippocampal slices. The mutated form of LGI1 fails to bind to ADAM22. ADAM22 is anchored to the postsynaptic density by cytoskeletal scaffolds containing stargazin. These studies in rat brain indicate possible avenues for understanding human epilepsy.

1 Laboratory of Genomics and Proteomics, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8522, Japan.
2 Department of Cellular and Molecular Pharmacology, University of California at San Francisco, San Francisco, CA 94143, USA.
3 Department of Integrative Biology, Eli Lilly and Company, Indianapolis, IN 46285, USA.
4 PRESTO, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan.

* To whom correspondence should be addressed. E-mail: fmasaki{at}nils.go.jp

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