首页> 外文期刊>The Journal of biological chemistry >E-cadherin Differentially Regulates the Assembly of Connexin43 and Connexin32 into Gap Junctions in Human Squamous Carcinoma Cells
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E-cadherin Differentially Regulates the Assembly of Connexin43 and Connexin32 into Gap Junctions in Human Squamous Carcinoma Cells

机译:E-cadherin差异地将Connexin43和Connexin32的组装调节到人鳞状癌细胞中的间隙结合中

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It is as yet unknown how the assembly of connexins (Cx) into gap junctions (GJ) is initiated upon cell-cell contact. We investigated whether the trafficking and assembly of Cx43 and Cx32 into GJs were contingent upon cell-cell adhesion mediated by E-cadherin. We also examined the role of the carboxyl termini of these Cxs in initiating the formation of GJs. Using cadherin and Cx-null cells, and by introducing Cx43 and Cx32, either alone or in combination with E-cadherin, our studies demonstrated that E-cadherin-mediated cell-cell adhesion was neither essential nor sufficient to initiate GJ assembly de novo in A431D human squamous carcinoma cells. However, E-cadherin facilitated the growth and assembly of preformed GJs composed of Cx43, although the growth of cells on Transwell filters was required to initiate the assembly of Cx32. Our results also documented that the carboxyl termini of both Cxs were required in this cell type to initiate the formation of GJs de novo. Our findings also showed that GJ puncta composed of Cx43 co-localized extensively with ZO-1 and actin fibers at cell peripheries and that ZO-1 knockdown attenuated Cx43 assembly. These findings suggest that the assembly of Cx43 and Cx32 into GJs is differentially modulated by E-cadherin-mediated cell-cell adhesion and that direct or indirect cross-talk between carboxyl tails of Cxs and actin cytoskeleton via ZO-1 may regulate GJ assembly and growth.
机译:它尚不赘述如何在细胞 - 细胞接触时开始如何将Connexins(CX)组装成间隙结合(GJ)。我们调查了CX43和CX32进入GJ的贩运和组装是否取决于通过E-Cadherin介导的细胞 - 细胞粘附。我们还研究了这些CXS的羧基末端在开始形成GJ时的作用。使用Cadherin和CX-Null细胞,并通过将CX43和CX32引入单独或与E-Cadherin组合,我们的研究表明,E-Cadherin介导的细胞 - 细胞粘附既不是必不可少的也不足以启动GJ集会De Novo A431D人鳞状癌细胞。然而,E-cadherin促进了由CX43组成的预制GJS的生长和组装,尽管需要在Transwell过滤器上的细胞生长开始CX32的组装。我们的结果还记录了这种细胞类型中需要两种CXS的羧基末端,以引发GJS De Novo的形成。我们的研究结果还表明,由CX43组成的GJ斑块与ZO-1共同定位,并在细胞周边的肌动蛋白纤维,ZO-1敲低衰减CX43组件。这些发现表明,CX43和CX32的组装成GJS通过E-Cadherin介导的细胞 - 细胞粘附差异调节,并且通过ZO-1的CXS和肌动蛋白细胞骨架的羧基尾部之间的直接或间接串扰可以调节GJ组装和生长。

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