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Significance This study addresses a fundamental question in neuroscience, namely how does the presynaptic component of the synapse precisely align with the postsynaptic component? This is essential for the proper transmission of signals across the synapse. This paper focuses on a set of transsynaptic, epilepsy-related proteins that are essential for this alignment. We show that the LGI1–ADAM22–MAGUK complex is a key player in the nanoarchitecture of the synapse, such that the release site is directly apposed to the nanocluster of glutamate receptors.

LGI1–ADAM22–MAGUK configures transsynaptic nanoalignment for synaptic transmission and epilepsy prevention