Molecular basis of junctional current rectification at an electrical synapse.

Shui, Yuan; Liu, Ping; Zhan, Haiying; Chen, Bojun; Wang, Zhao-Wen · Sci Adv · 2020

basic_science · Level V

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Abstract

Rectifying electrical synapses (RESs) exist across animal species, but their rectification mechanism is largely unknown. We investigated why RESs between AVA premotor interneurons and A-type cholinergic motoneurons (A-MNs) in <i>Caenorhabditis elegans</i> escape circuit conduct junctional currents (<i>I</i> <sub>j</sub>) only in the antidromic direction. These RESs consist of UNC-7 innexin in AVA and UNC-9 innexin in A-MNs. UNC-7 has multiple isoforms differing in the length and sequence of the amino terminus. In a heterologous expression system, only one UNC-7 isoform, UNC-7b, can form heterotypic gap junctions (GJs) with UNC-9 that strongly favor <i>I</i> <sub>j</sub> in the UNC-9 to UNC-7 direction. Knockout of <i>unc-7b</i> alone almost eliminated the <i>I</i> <sub>j</sub>, whereas AVA-specific expression of UNC-7b substantially rescued the coupling defect of <i>unc-7</i> mutant. Neutralizing charged residues in UNC-7b amino terminus abolished the rectification property of UNC-7b/UNC-9 GJs. Our results suggest that the rectification property results from electrostatic interactions between charged residues in UNC-7b amino terminus.