Neurobeachin Is Required Postsynaptically for Electrical and Chemical Synapse Formation

Abstract

Neural networks and their function are defined by synapses, which are adhesions specialized for intercellular communication that can be either chemical or electrical. At chemical synapses, transmission between neurons is mediated by neurotransmitters, whereas at electrical synapses, direct ionic and metabolic coupling occur via gap junctions between neurons. The molecular pathways required for electrical synaptogenesis are not well understood, and whether they share mechanisms of formation with chemical synapses is not clear. Here, using a forward genetic screen in zebrafish, we find that the autism-associated gene neurobeachin (nbea), which encodes a BEACH-domain-containing protein implicated in endomembrane trafficking, is required for both electrical and chemical synapse formation. Additionally, we find that nbea is dispensable for axonal formation and early dendritic outgrowth but is required to maintain dendritic complexity. These synaptic and morphological defects correlate with deficiencies in behavioral performance. Using chimeric animals in which individually identifiable neurons are either mutant or wild-type, we find that Nbea is necessary and sufficient autonomously in the postsynaptic neuron for both synapse formation and dendritic arborization. Our data identify a surprising link between electrical and chemical synapse formation and show that Nbea acts as a critical regulator in the postsynaptic neuron for the coordination of dendritic morphology with synaptogenesis.