Department of Physiology and Pathophysiology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.
Department of Physiology and Pathophysiology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.
Neuroscience. 2018 Aug 1;384:241-261. doi: 10.1016/j.neuroscience.2018.05.026. Epub 2018 Jun 5.
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.
缝隙连接和黏附连接之间的密切结构和功能关系已在周围组织中得到证实,但在中枢神经系统中尚未得到彻底研究,在中枢神经系统中,黏附连接通常与神经元缝隙连接紧密相邻。在这里,我们使用免疫荧光方法来记录各种黏附连接蛋白成分的定位与我们之前报道的发生在由神经元缝隙连接组成的电突触中的蛋白成分的定位之间的关系,这些神经元缝隙连接由连接蛋白 36(Cx36)组成。在几个检查的脑区中,黏附连接成分 N-钙黏蛋白和 nectin-1 经常被发现定位于含有 Cx36 的缝隙连接附近或与之重叠。这同样适用于黏附连接相关蛋白α-连环蛋白和β-连环蛋白,以及紧密连接蛋白-1 和 AF6(又名 afadin),它们被报道是黏附连接和缝隙连接的组成部分。这些连接的蛋白成分的部署在中脑三叉神经核(MesV)中的初级传入神经元之间的体接触处尤为明显,在 Cx36 缺失小鼠中,黏附连接的结构成分似乎得到了维持。这些结果支持了关于电突触的多分子组成的新观点,并为现在可以被认为是黏附连接-神经元缝隙连接复合体的各种结构和功能的蛋白-蛋白相互作用提供了可能性。此外,这些结果指向了细胞内信号通路,这些通路可能有助于该复合体的组装、维持和周转,以及电突触处神经元通讯的动态性质。
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