TY - JOUR TI - Electrical synaptic transmission requires a postsynaptic scaffolding protein AU - Lasseigne, Abagael M AU - Echeverry, Fabio A AU - Ijaz, Sundas AU - Michel, Jennifer Carlisle AU - Martin, E Anne AU - Marsh, Audrey J AU - Trujillo, Elisa AU - Marsden, Kurt C AU - Pereda, Alberto E AU - Miller, Adam C A2 - Hobert, Oliver A2 - Chen, Lu VL - 10 PY - 2021 DA - 2021/04/28 SP - e66898 C1 - eLife 2021;10:e66898 DO - 10.7554/eLife.66898 UR - https://doi.org/10.7554/eLife.66898 AB - Electrical synaptic transmission relies on neuronal gap junctions containing channels constructed by Connexins. While at chemical synapses neurotransmitter-gated ion channels are critically supported by scaffolding proteins, it is unknown if channels at electrical synapses require similar scaffold support. Here, we investigated the functional relationship between neuronal Connexins and Zonula Occludens 1 (ZO1), an intracellular scaffolding protein localized to electrical synapses. Using model electrical synapses in zebrafish Mauthner cells, we demonstrated that ZO1 is required for robust synaptic Connexin localization, but Connexins are dispensable for ZO1 localization. Disrupting this hierarchical ZO1/Connexin relationship abolishes electrical transmission and disrupts Mauthner cell-initiated escape responses. We found that ZO1 is asymmetrically localized exclusively postsynaptically at neuronal contacts where it functions to assemble intercellular channels. Thus, forming functional neuronal gap junctions requires a postsynaptic scaffolding protein. The critical function of a scaffolding molecule reveals an unanticipated complexity of molecular and functional organization at electrical synapses. KW - electrical synapse KW - gap junctions KW - connexins KW - zo1 zo-1 KW - synapse formation KW - electrical coupling JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -