Cadherin Clusters and actin filaments

钙粘素聚集是介导和控制细胞间黏附的一种独特的分子过程。在……里面 此外，它还调节肌动蛋白的细胞骨架、极性、增殖和其他结构。 和信号通路。钙粘附素簇加强了脆弱的个体粘附性，并产生了 起作用的细胞-细胞黏附连接。通过连接到F-肌动蛋白，他们确定了整个组织 和肌动蛋白细胞骨架的动力学。最后，它们为不同的组织提供了特定的结构支架 信号通路。尽管这些令人难以置信的重要功能，显然在几乎 组织形态发生的方方面面、钙粘附素的分子机制及其调控 聚集性还有待研究。这项提议将阐明钙粘素簇是如何形成的以及如何形成的 它们参与了如此多样化的细胞机制。 根据这一提案在前几年所做的工作表明，主要的粘连(AJ) 脊椎动物中的细胞-细胞黏附结构，由许多短暂但高度黏附的结构组成 钙粘素纳米簇。每一团簇的短寿命使AJS具有粘附性和柔韧性 时间到了。这些星系团的不断产生显然是基于一种显著的反应-- 钙粘蛋白相关蛋白α-连环蛋白与肌动蛋白细丝的协同结合。该集会- 钙粘附素簇和相关的F-肌动蛋白的分解循环因此紧密耦合 相邻细胞中钙粘附素和肌动蛋白动力学的同步。最后，我们发现钙粘附素簇 可以通过钙粘附素/连环蛋白结合蛋白在结构上多样化。钙粘附素的多样化 聚集是基于这样一个事实，即这些蛋白质中的每一种都提供了侧向钙粘附素的特定模式- 钙粘附素相互作用。这些相互作用的各种结果形成了一组不同的星团 其中每一个可能都有特定的功能。钙粘素聚集素的研究进展 请允许我们提出这一建议，其中包括：(I)钙粘附素在聚集和 信号蛋白Erbin和适配蛋白PLEKHA5的功能；(Ii)分子 细胞外钙粘蛋白结合事件与α-连环蛋白与F-肌动蛋白结合的机制； 以及(Iii)钙粘附素聚集在一些组织形态发生的例子中的作用。

Cadherin clustering is a unique molecular process that mediates and controls cell-cell adhesion. In addition, it also regulates the actin cytoskeleton, polarity, proliferation, and apparently other structures and signaling pathways. Cadherin clusters reinforce weak individual adhesive bonds and generate functional cell-cell adhesion links. By connecting to F-actin, they determine the overall organization and dynamics of the actin cytoskeleton. Finally, they provide specific structural scaffolds for various signaling pathways. Despite such incredibly important functions, which obviously play out in nearly every aspect of tissue morphogenesis, the molecular mechanisms and regulation of cadherin clustering remains to be studied. This proposal will shed light on how cadherin clusters form and how they participate in such diverse array of cellular mechanisms. The work done under this proposal in previous years showed that adherens junctions (AJs), the major cell-cell adhesion structures in vertebrates, consist of numerous transient but highly adhesive cadherin nanoclusters. The short lifetime of each cluster makes AJs adhesive and flexible at the same time. The continuous generation of these clusters is apparently based on a remarkable reaction – cooperative binding of the cadherin-associated protein α-catenin to actin filaments. The assembly- disassembly cycles of both cadherin clusters and associated F-actin are tightly coupled thereby synchronizing cadherin and actin dynamics in adjacent cells. Finally, we found that cadherin clusters could be structurally diversified by cadherin/catenin-bound proteins. Diversification of cadherin clustering is based on the fact that each of these proteins provides specific modes of lateral cadherin- cadherin interactions. A variety of these interactions results in formation of an array of distinct clusters each of which might have particular functions. The advances in understanding cadherin clustering allow us to come up with this proposal, which includes: (i) the role of cadherin in clustering and function of two proteins, signaling protein Erbin, and adaptor protein PLEKHA5; (ii) molecular mechanisms interconnecting extracellular cadherin binding events with α-catenin-binding to F-actin; and (iii) the role of cadherin clustering in some examples of tissue morphogenesis.