| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2017: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Outline of Final Research Achievements |
Regulated trans-synaptic communication plays a pivotal role in synaptic transmission. Although recent studies have identified a large number of synaptic adhesion molecules, the molecular mechanism for trans-synaptic communication remains incompletely understood. In this study, we showed the crystal structure of human LGI1-ADAM22 complex, revealing a 2:2 heterotetrameric assembly through the intermolecular LGI1-LGI1 interaction. A pathogenic R474Q mutation of LGI1 is located in the LGI1-LGI1 interface and disrupts the higher-order assembly of the LGI1-ADAM22 complex in vitro and in a mouse model for familial epilepsy. These studies support the notion that the LGI1-ADAM22 complex functions as the trans-synaptic machinery for precise synaptic transmission and disruption of this linkage causes the epileptic disorder.
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