Asymmetry of an Intracellular Scaffold at Vertebrate Electrical Synapses

Neuronal synaptic connections are either chemical or electrical, and these two types of synapses work together to dynamically define neural circuit function [1]. Although we know a great deal about the molecules that support chemical synapse formation and function, we know little about the macromolecular complexes that regulate electrical synapses. Electrical synapses are created by gap junction (GJ) channels that provide direct ionic communication between neurons [2]. Although they are often molecularly and functionally symmetric, recent work has found that pre-and postsynaptic neurons can contribute different GJ-forming proteins, creating molecularly asymmetric channels that are correlated with functional asymmetry at the synapse [3, 4]. Associated with the GJs are structures observed by electron microscopy termed the electrical synapse density (ESD) [5]. The ESD has been suggested to be critical for the formation and function of the electrical synapse, yet the biochemical makeup of these structures is poorly understood. Here we find that electrical synapse formation in vivo requires an intracellular scaffold called Tight Junction Protein 1b (Tjp1b). Tjp1b is localized to the electrical synapse, where it is required for the stabilization of the GJs and for electrical synapse function. Strikingly, we find that Tjp1b protein localizes and functions asymmetrically, exclusively on the postsynaptic side of the synapse. Our findings support a novel model of electrical synapse molecular asymmetry at the level of an intracellular scaffold that is required for building the electrical synapse. We propose that such ESD asymmetries could be used by all nervous systems to support molecular and functional asymmetries at electrical synapses.