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Science Sep (2006); 313(5794):1792-5
Epilepsy-related ligand-receptor complex LGI1 and ADAM22 regulate synaptic transmission-
Fukata Y, Adesnik H, Iwanaga T, Bredt DS, Nicoll RA, Fukata M
Laboratory of Genomics and Proteomics, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8522, Japan-
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-
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Chris Stark, Bobby-Joe Breitkreutz, Teresa Reguly, Lorrie Boucher, Ashton Breitkreutz, Mike Tyers.
Nucleic Acids Res. Jan 1;34:D535-9.