LGI1–ADAM22–MAGUK configures transsynaptic nanoalignment for synaptic transmission and epilepsy prevention
Yuko Fukata, Xiumin Chen, Satomi Chiken, Yoko Hirano, Atsushi Yamagata, Hiroki Inahashi, Makoto Sanbo, Hiromi Sano, Teppei Goto, Masumi Hirabayashi, Hans‐Christian Kornau, Harald Prüß, Atsushi Nambu, Shuya Fukai, Roger A. Nicoll, Masaki Fukata
Abstract
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.