Structural and Intermolecular Associations Between Connexin36 and Protein Components of the Adherens Junction–Neuronal Gap Junction Complex. (1st August 2018) - Nagy, J.I.
Graphical abstract: Highlights: Neuronal gap junctions in brain are closely associated with adherens junctions. N-cadherin and nectin-1 are localized adjacent to connexin36-containing gap junctions. Scaffolding between adherens junctions and gap junctions may be provided by catenins and AF6. Electrical synapses consist of a multi-molecular adherens junction-neuronal gap junction complex. Components of that complex may be targets for intracellular signalling via SynGAP1 and Rap1. Abstract: Intimate structural and functional relationships between gap junctions and adherens junctions have been demonstrated in peripheral tissues, but have not been thoroughly examined in the central nervous system, where adherens junctions are often found in close proximity to neuronal gap junctions. Here, we used immunofluorescence approaches to document the localization of various protein components of adherens junctions in relation to those that we have previously reported to occur at electrical synapses formed by neuronal gap junctions composed of connexin36 (Cx36). The adherens junction constituents N-cadherin and nectin-1 were frequently found to localize near or overlap with Cx36-containing gap junctions in several brain regions examined. This was also true of the adherens junction-associated proteins α-catenin and β-catenin, as well as the proteins zonula occludens-1 and AF6 (aka, afadin) that were reported constituents of both adherens junctions and gap junctions. The deployment of the protein constituents of these junctions was especially striking at somatic contacts between primary afferent neurons in the mesencephalic trigeminal nucleus (MesV), where the structural components of adherens junctions appeared to be maintained in connexin36 null mice. These results support emerging views concerning the multi-molecular composition of electrical synapses and raise possibilities for various structural and functional protein–protein interactions at what now can be considered the adherens junction–neuronal gap junction complex. Further, the results point to intracellular signaling pathways that could potentially contribute to the assembly, maintenance and turnover of this complex, as well as to the dynamic nature of neuronal communication at electrical synapses.