Abstract
Brain function relies upon the carefully coordinated development of specialized synaptic connections between neurons. The subcellular positioning of synapses and their molecular composition regulate neural computation, forming the fundamental basis of neural circuits. Like chemical synapses, electrical synapses are constructed from an assortment of cell adhesion, scaffolding, and regulatory molecules, as well as channel-forming Connexin proteins, yet little is known about how these molecules localize at specified subcellular compartments of the neuron. Here we investigated the cell biological relationship between the autism- and epilepsy-associated gene Neurobeachin, the gap junction forming neuronal Connexins, and electrical synapse scaffold Zonula Occludens 1 (ZO1). Using the model electrical synapses of the zebrafish Mauthner circuit we found that Neurobeachin localizes to the electrical synapse independent of the ZO1 scaffold and Connexins. By contrast, we show that Neurobeachin functions postsynaptically where it is required for the robust localization of ZO1 and Connexins. We demonstrate that Neurobeachin binds ZO1 but not Connexin proteins. Finally, we find that Neurobeachin is required to restrict postsynaptic electrical synapse proteins to dendritic synapses. Altogether the findings reveal a mechanism for the asymmetric synaptic localization of electrical synapse components providing a basis for the subcellular specialization of neuronal gap junctions.
Competing Interest Statement
The authors have declared no competing interest.