The dynamic Nexus: gap junctions control protein localization and mobility in distinct and surprising ways.
The dynamic Nexus: gap junctions control protein localization and mobility in distinct and surprising ways.
复制标题
DOI：
10.1038/s41598-020-73892-6
复制
发表时间：
2020-10-12
影响因子：
4.6
通讯作者：
Spray DC
中科院分区：
文献类型：
--
作者：
McCutcheon S;Stout RF Jr;Spray DC
间隙连接（GJ）通道允许分子，如离子，代谢物和第二信使，在细胞之间转移。它们的功能对许多细胞相互作用至关重要，提供代谢物、信号分子和离子电流的交换。GJ通道由连接蛋白（Cx）六聚体在细胞外空间配对组成，通常在细胞相邻处形成大的簇状通道筏，称为斑块。x - x与与GJ通道相互作用的分子一起构成了被称为GJ Nexus的超分子结构。虽然已经研究了GJ斑块中连接蛋白定位的稳定性，但其他Nexus成分的移动性尚未得到解决。对几种nexus组分和其他膜蛋白的共定位分析显示，某些分子被排除在GJ斑块之外（水通道蛋白4，EAAT2b），而其他分子则具有相当的渗透性（亲脂分子，Cx30, ZO-1, Occludin）。标记的nexus相关蛋白在光漂白后的荧光恢复表明，斑块区域的流动性受到Cx蛋白流动性的影响。这些新发现表明，GJ Nexus是一个动态的膜细胞器，细胞质和膜嵌入蛋白根据不同的参数结合和扩散。
Gap junction (GJ) channels permit molecules, such as ions, metabolites and second messengers, to transfer between cells. Their function is critical for numerous cellular interactions, providing exchange of metabolites, signaling molecules, and ionic currents. GJ channels are composed of Connexin (Cx) hexamers paired across extracellular space and typically form large rafts of clustered channels, called plaques, at cell appositions. Cxs together with molecules that interact with GJ channels make up a supramolecular structure known as the GJ Nexus. While the stability of connexin localization in GJ plaques has been studied, mobility of other Nexus components has yet to be addressed. Colocalization analysis of several nexus components and other membrane proteins reveal that certain molecules are excluded from the GJ plaque (Aquaporin 4, EAAT2b), while others are quite penetrant (lipophilic molecules, Cx30, ZO-1, Occludin). Fluorescence recovery after photobleaching of tagged Nexus-associated proteins showed that mobility in plaque domains is affected by mobility of the Cx proteins. These novel findings indicate that the GJ Nexus is a dynamic membrane organelle, with cytoplasmic and membrane-embedded proteins binding and diffusing according to distinct parameters.
登录
查看更多内容
影响因子：
3.3
作者：
Genoud, C.;Houades, V.;Giaume, C.
通讯作者：
Giaume, C.
影响因子：
15.9
作者：
Horng, Sam;Therattil, Anthony;John, Gareth R.
通讯作者：
John, Gareth R.
影响因子：
4
作者：
Kelly, John J.;Shao, Qing;Laird, Dale W.
通讯作者：
Laird, Dale W.
影响因子：
6.2
作者：
Alvarez JI;Katayama T;Prat A
通讯作者：
Prat A
影响因子：
5.3
作者：
Cina, Cima;Maass, Karen;Naus, Christian C.
通讯作者：
Naus, Christian C.