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-