Epilepsy-related ligand/receptor complex LGI1 and ADAM22 regulate synaptic transmission

被引:301
作者
Fukata, Yuko
Adesnik, Hillel
Iwanaga, Tsuyoshi
Bredt, David S.
Nicoll, Roger A.
Fukata, Masaki [1 ]
机构
[1] Natl Ctr Geriatr & Gerontol, Natl Inst Longev Sci, Lab Genom & Proteom, Aichi 4748522, Japan
[2] Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94143 USA
[3] Eli Lilly & Co, Dept Integrat Biol, Indianapolis, IN 46285 USA
[4] Japan Sci & Technol Agcy, PRESTO, Kawaguchi, Saitama 3320012, Japan
关键词
D O I
10.1126/science.1129947
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:1792 / 1795
页数:4
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