Cadherin Clusters and actin filaments

钙粘蛋白簇和肌动蛋白丝

• 批准号: 10366391
• 负责人: Sergey M Troyanovsky
• 金额: $ 46.23万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10366391
• 关键词: Actins; Adaptor Signaling Protein; Adherens Junction; Adhesions; Adhesives; Amaze; Binding; Binding Proteins; Cadherins; Cell Polarity; Cell-Cell Adhesion; Cells; Complex; Coupled; Cytoskeleton; Data; Development; Event; F-Actin; Foundations; Generations; Individual; Lateral; Light; Link; Liquid substance; Mediating; Medicine; Microfilaments; Molecular; Morphogenesis; Pharmacology; Play; Process; Proteins; Radial; Reaction; Regulation; Role; Signal Pathway; Signal Transduction; Signaling Protein; Stratification; Structure; Testing; Time; Tissues; Vertebrates; Work; alpha catenin; base; cell motility; design; experimental study; extracellular; flexibility; in vitro Model; in vivo; intercalation; mutant; nanocluster; novel; practical application; recruit; scaffold; solid state

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.

钙粘蛋白簇是介导和控制细胞间粘附的独特分子过程。在 此外，它还调节肌动蛋白细胞骨架、极性、增殖和明显的其他结构 和信号通路。钙粘蛋白簇增强了弱的个体粘合键并产生 功能性细胞间粘附连接。通过连接 F-肌动蛋白，它们决定了整体组织 和肌动蛋白细胞骨架的动力学。最后，他们为各种用途提供了特定的结构支架 信号通路。尽管有如此极其重要的功能，但它们显然在近乎发挥作用 组织形态发生的各个方面、钙粘蛋白的分子机制和调节 聚类还有待研究。该提案将阐明钙粘蛋白簇如何形成以及如何形成 它们参与多种不同的细胞机制。 前几年根据该提案所做的工作表明，粘附连接（AJ）是主要的 脊椎动物的细胞与细胞粘附结构由许多短暂但高度粘附的结构组成 钙粘蛋白纳米簇。每个簇的寿命较短，使得 AJ 同时具有粘合性和灵活性 时间。这些簇的不断产生显然是基于一种显着的反应—— 钙粘蛋白相关蛋白 α-连环蛋白与肌动蛋白丝的协同结合。大会—— 钙粘蛋白簇和相关 F-肌动蛋白的分解周期因此紧密耦合 同步相邻细胞中的钙粘蛋白和肌动蛋白动力学。最后，我们发现钙粘蛋白簇 可以通过钙粘蛋白/连环蛋白结合蛋白进行结构多样化。钙粘蛋白多样化 聚类基于以下事实：这些蛋白质中的每一种都提供横向钙粘蛋白的特定模式 钙粘蛋白相互作用。各种相互作用导致形成一系列不同的簇 其中每一个都可能具有特定的功能。了解钙粘蛋白聚类的进展 让我们提出这个建议，其中包括：（i）钙粘蛋白在聚类和 信号蛋白 Erbin 和接头蛋白 PLEKHA5 两种蛋白的功能； (二) 分子 细胞外钙粘蛋白结合事件与 α-连环蛋白与 F-肌动蛋白的结合相互关联的机制； (iii)钙粘蛋白簇在组织形态发生的一些例子中的作用。