دورية أكاديمية
LGI1–ADAM22–MAGUK configures transsynaptic nanoalignment for synaptic transmission and epilepsy prevention
| العنوان: | LGI1–ADAM22–MAGUK configures transsynaptic nanoalignment for synaptic transmission and epilepsy prevention |
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| المؤلفون: | Fukata, Yuko, Chen, Xiumin, Chiken, Satomi, Hirano, Yoko, Yamagata, Atsushi, Inahashi, Hiroki, Sanbo, Makoto, Sano, Hiromi, Goto, Teppei, Hirabayashi, Masumi, Kornau, Hans-Christian, Prüss, Harald, Nambu, Atsushi, Fukai, Shuya, Nicoll, Roger A., Fukata, Masaki |
| المساهمون: | 深田, 優子, 知見, 聡美, 平野, 瑶子, 山形, 敦史, 稲橋, 宏樹, 三宝, 誠, 佐野, 裕美, 後藤, 鉄平, 平林, 眞澄, 南部, 篤, 深井, 周也, 深田, 正紀, 10361792 |
| بيانات النشر: | National Academy of Sciences |
| سنة النشر: | 2021 |
| المجموعة: | Kyoto University Research Information Repository (KURENAI) / 京都大学学術情報リポジトリ |
| مصطلحات موضوعية: | LGI1–ADAM22, MAGUK, AMPA receptor, transsynaptic nanocolumn, epilepsy |
| الوصف: | Physiological functioning and homeostasis of the brain rely on finely tuned synaptic transmission, which involves nanoscale alignment between presynaptic neurotransmitter-release machinery and postsynaptic receptors. However, the molecular identity and physiological significance of transsynaptic nanoalignment remain incompletely understood. Here, we report that epilepsy gene products, a secreted protein LGI1 and its receptor ADAM22, govern transsynaptic nanoalignment to prevent epilepsy. We found that LGI1–ADAM22 instructs PSD-95 family membrane-associated guanylate kinases (MAGUKs) to organize transsynaptic protein networks, including NMDA/AMPA receptors, Kv1 channels, and LRRTM4–Neurexin adhesion molecules. Adam22ΔC5/ΔC5 knock-in mice devoid of the ADAM22–MAGUK interaction display lethal epilepsy of hippocampal origin, representing the mouse model for ADAM22-related epileptic encephalopathy. This model shows less-condensed PSD-95 nanodomains, disordered transsynaptic nanoalignment, and decreased excitatory synaptic transmission in the hippocampus. Strikingly, without ADAM22 binding, PSD-95 cannot potentiate AMPA receptor-mediated synaptic transmission. Furthermore, forced coexpression of ADAM22 and PSD-95 reconstitutes nano-condensates in nonneuronal cells. Collectively, this study reveals LGI1–ADAM22–MAGUK as an essential component of transsynaptic nanoarchitecture for precise synaptic transmission and epilepsy prevention. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | Japanese |
| تدمد: | 0027-8424 1091-6490 |
| العلاقة: | http://hdl.handle.net/2433/261902Test; Proceedings of the National Academy of Sciences of the United States of America; 118; e2022580118 |
| الإتاحة: | http://hdl.handle.net/2433/261902Test |
| حقوق: | © 2021 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND). |
| رقم الانضمام: | edsbas.502BE7D3 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 00278424 10916490 |
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