Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
J Invest Dermatol. 2013 Nov;133(11):2546-2554. doi: 10.1038/jid.2013.200. Epub 2013 May 2.
Cadherin and nectin are distinct transmembrane proteins of adherens junctions. Their ectodomains mediate adhesion, whereas their cytosolic regions couple the adhesive contact to the cytoskeleton. Both these proteins are essential for adherens junction formation and maintenance. However, some basic aspects of these proteins, such as their organization in adherence junctions, have remained open. Therefore, using super-resolution microscopy and live imaging, we focused on the subjunctional distribution of these proteins. We showed that cadherin and nectin in the junctions of A431 cells and human keratinocytes are located in separate clusters. The size of each cluster is independent of that of the adjacent clusters and can significantly fluctuate over time. Several nectin and cadherin clusters that constitute an individual adherens junction are united by the same actin-filament bundle. Surprisingly, interactions between each cluster and F-actin are not uniform, as neither vinculin nor LIM-domain actin-binding proteins match the boundaries of cadherin or nectin clusters. Thus, the adherens junction is not a uniform structure but a mosaic of different adhesive units with very diverse modes of interaction with the cytoskeleton. We propose that such a mosaic architecture of adherence junctions is important for the fast regulation of their dynamics.
钙黏蛋白和 nectin 是黏着连接的两种不同的跨膜蛋白。它们的细胞外结构域介导黏附，而其细胞内结构域将黏附接触与细胞骨架偶联。这两种蛋白对于黏着连接的形成和维持都是必需的。然而，这些蛋白的一些基本方面，如它们在黏附连接中的组织方式，仍然存在争议。因此，我们使用超分辨率显微镜和活细胞成像技术，专注于这些蛋白在亚连接区的分布。我们发现，A431 细胞和人角质形成细胞连接中的钙黏蛋白和 nectin 位于不同的簇中。每个簇的大小与其相邻簇无关，并且可以随时间显著波动。构成单个黏着连接的几个 nectin 和 cadherin 簇由相同的肌动蛋白丝束连接。令人惊讶的是，每个簇与 F-actin 之间的相互作用并不均匀，因为 vinculin 和 LIM 结构域肌动蛋白结合蛋白都不符合 cadherin 或 nectin 簇的边界。因此，黏着连接不是一个均匀的结构，而是由不同的黏附单元组成的镶嵌结构，与细胞骨架的相互作用方式非常多样化。我们提出，黏着连接的这种镶嵌结构对于其动力学的快速调节非常重要。
