气候变化领域集成服务门户(CCPortal): LGI1–ADAM22–MAGUK configures transsynaptic nanoalignment for synaptic transmission and epilepsy prevention

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DOI	10.1073/pnas.2022580118
	LGI1–ADAM22–MAGUK configures transsynaptic nanoalignment for synaptic transmission and epilepsy prevention
	Fukata Y.; Chen X.; Chiken S.; Hirano Y.; Yamagata A.; Inahashi H.; Sanbo M.; Sano H.; Goto T.; Hirabayashi M.; Kornau H.-C.; Prüss H.; Nambu A.; Fukai S.; Nicoll R.A.; Fukata M.
发表日期	2021
ISSN	00278424
卷号	118 期号:3
英文摘要	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. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	LGI1–ADAM22 \| MAGUK \| AMPA receptor \| transsynaptic nanocolumn \| epilepsy
语种	英语
scopus关键词	ADAM 22 protein; ADAM protein; AMPA receptor; disks large homolog 4; LGI1 protein; membrane associated guanylate kinase; n methyl dextro aspartic acid; potassium channel Kv1.1; unclassified drug; animal experiment; Article; brain disease; controlled study; electroencephalogram; epilepsy; excitatory junction potential; hippocampus; human; mouse; nonhuman; priority journal; protein expression; protein protein interaction; synaptic transmission
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180992
作者单位	Division of Membrane Physiology, Department of Molecular and Cellular Physiology, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Aichi, 444-8787, Japan; Department of Physiological Sciences, School of Life Science, SOKENDAI (The Graduate University for Advanced Studies), Aichi, 444-8585, Japan; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, United States; Department of Physiology, University of California, San Francisco, CA 94158, United States; Division of System Neurophysiology, Department of System Neuroscience, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Aichi, 444-8585, Japan; Department of Pediatrics, Graduate School of Medicine, University of Tokyo, Tokyo, 113-8655, Japan; Laboratory for Protein Functional and Structural Biology, RIKEN Center for Biosystems Dynamics Research, Kanagawa, 230-0045, Japan; Center for Genetic Analysis of Behavior, National Institu...
推荐引用方式 GB/T 7714	Fukata Y.,Chen X.,Chiken S.,等. LGI1–ADAM22–MAGUK configures transsynaptic nanoalignment for synaptic transmission and epilepsy prevention[J],2021,118(3).
APA	Fukata Y..,Chen X..,Chiken S..,Hirano Y..,Yamagata A..,...&Fukata M..(2021).LGI1–ADAM22–MAGUK configures transsynaptic nanoalignment for synaptic transmission and epilepsy prevention.Proceedings of the National Academy of Sciences of the United States of America,118(3).
MLA	Fukata Y.,et al."LGI1–ADAM22–MAGUK configures transsynaptic nanoalignment for synaptic transmission and epilepsy prevention".Proceedings of the National Academy of Sciences of the United States of America 118.3(2021).