Development of artificial synapse organizers liganded with a peptide tag for molecularly inducible neuron-microelectrode interface.

It has been proposed that cell-type-specific bioelectronic interfaces for neuronal circuits could be established by utilizing the function of synapse organizers. For this purpose, using neurexin-1β and a peptide tag, we engineered compact synapse organizers that do not interact with the naturally occurring receptors but induce presynaptic differentiation upon contact with nanobody-decorated objects in cultured mammalian and chick forebrain neurons. In chick neurons, the engineered organizer exerted synaptogenesis typically in ∼4 h after the contact, even under an air atmosphere at room temperature, thereby providing a useful cellular model for establishing the molecularly inducible neuron-microelectrode interface.

Epitope-tag-mediated synaptogenic activity in an engineered neurexin-1β lacking the binding interface with neuroligin-1.

Clustering of neurexin-1β occurs through the formation of a trans-cellular complex with neuroligin-1, which promotes the generation of presynapse. While the extracellular region of neurexin-1β functions to constitute the heterophilic binding interface with neuroligin-1, it has remained unclear whether the region could also play any key role in exerting the intracellular signaling for presynaptic differentiation. In this study, we generated neurexin-1β lacking the binding site to neuroligin-1 and with a FLAG epitope at the N-terminus, and examined its activity in cultured neurons.