Neurobeachin controls the asymmetric subcellular distribution of electrical synapse proteins

The subcellular positioning of synapses and their specialized molecular compositions form the fundamental basis of neural circuits. Like chemical synapses, electrical synapses are constructed from an assortment of adhesion, scaffolding, and regulatory molecules, yet little is known about how these molecules localize at specified subcellular neuronal compartments. Here we investigated the relationship between the autism- and epilepsy-associated gene Neurobeachin, neuronal gap junction channelforming Connexins, and the scaffold ZO1. Using the zebrafish Mauthner circuit we found Neurobeachin localizes to the electrical synapse independent of ZO1 and Connexins. By contrast, we show Neurobeachin is required postsynaptically for the robust localization of ZO1 and Connexins. We demonstrate Neurobeachin binds ZO1 but not Connexins. Finally, we find Neurobeachin is required to restrict postsynaptic electrical synapse proteins to dendrites. These findings reveal a mechanism for the asymmetric synaptic localization of electrical synapse components providing a basis for the subcellular specialization of neuronal gap junctions.