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Under Construction: Building the Macromolecular Superstructure and Signaling Components of an Electrical Synapse

机译:正在建设中:构建电气突触的大分子超标结构和信号传导组件

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摘要

A great deal is now known about the protein components of tight junctions and adherens junctions, as well as how these are assembled. Less is known about the molecular framework of gap junctions, but these also have membrane specializations and are subject to regulation of their assembly and turnover. Thus, it is reasonable to consider that these three types of junctions may share macromolecular commonalities. Indeed, the tight junction scaffolding protein zonula occluden-1 (ZO-1) is also present at adherens and gap junctions, including neuronal gap junctions. On the basis of these earlier observations, we more recently found that two additional proteins, AF6 and MUPP1, known to be associated with ZO-1 at tight and adherens junctions, are also components of neuronal gap junctions in rodent brain and directly interact with connexin36 (Cx36) that forms these junctions. Here, we show by immunofluorescence labeling that the cytoskeletal-associated protein cingulin, commonly found at tight junctions, is also localized at neuronal gap junctions throughout the central nervous system. In consideration of known functions related to ZO-1, AF6, MUPP1, and cingulin, our results provide a context in which to examine functional relationships between these proteins at Cx36- containing electrical synapses in brain—specifically, how they may contribute to regulation of transmission at these synapses, and how they may govern gap junction channel assembly and/or disassembly.
机译:现在已经了解了紧密连接和粘附结的蛋白质成分以及这些蛋白质成分以及这些都是如何组装的。较少关于间隙交叉点的分子骨架,但这些也具有膜专业,并受其组装和营业额的规定。因此,考虑这三种类型的结可以共享大分子公共性是合理的。实际上,紧密结脚骨折蛋白质毒蛋白occluden-1(ZO-1)也存在于包括神经元间隙连接点的粘附和间隙连接点。在这些早期的观察结果的基础上,我们最近发现,已知在紧密和粘附的连接点与ZO-1相关的另外两种蛋白质,AF6和MUPP1,也是啮齿动物脑中神经元间隙连接的组分,并直接与Connexin36相互作用(CX36)形成这些连接点。在这里,我们通过免疫荧光标记显示,即常见于紧密交叉点的细胞骨骼相关蛋白曲线也在整个中枢神经系统的神经元间隙连接处局部化。考虑到与ZO-1,AF6,MUPP1和Cingulin相关的已知功能,我们的结果提供了一种上下文,其中在大脑中含有CX36的电气突触的含有CX36的电突触之间的功能关系 - 具体而言,它们可能有助于调节这些蛋白质在这些突触处传输,以及它们如何控制间隙结沟道组件和/或拆卸。

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