Electrical synaptic transmission requires a postsynaptic scaffolding protein.

Abagael M Lasseigne,Fabio A Echeverry,Jennifer Carlisle Michel,Audrey J Marsh,Adam C Miller,Elisa Trujillo,Sundas Ijaz,E Anne Martin,Alberto E Pereda,Kurt C Marsden

doi:10.7554/elife.66898

Abstract

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.

Highlights

Synapses are specialized cellular adhesions between neurons that rapidly transfer information to facilitate neural network function
We focus on two populations of stereotyped electrical synapses made by Mauthner cells: (1) ‘club ending’ (CE) synapses (Bartelmez and Hoerr, 1933; Pereda et al, 2004; Yao et al, 2014), which are mixed electrical/glutamatergic chemical synaptic contacts formed between auditory afferents of the eighth cranial nerve and the Mauthner cell’s lateral dendrite (Figure 1A,B) and (2) en passant electrical synapses formed between the Mauthner axon and Commissural Local (CoLo) interneurons found in each spinal-cord segment (Figure 1A,M/ CoLo synapses) (Satou et al, 2009)
We propose that electrical synapses likely constitute complex and asymmetric synaptic structures with features that parallel the molecular and functional organization of the postsynaptic density’ (PSD) at chemical synapses

Summary

Introduction

Synapses are specialized cellular adhesions between neurons that rapidly transfer information to facilitate neural network function. Chemical synapses are inherently asymmetric structures, derived from presynaptic specializations that regulate the release of neurotransmitters and postsynaptic specializations that contain neurotransmitter receptors and the machinery required to propagate signal transmission. Both specializations require hundreds to thousands of proteins, which together tightly control the structure, function, and modulation of synaptic communication (Ackermann et al, 2015; Grant, 2019; Siddiqui and Craig, 2011). While multiple Connexins and Innexins can contribute to individual electrical synapses

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