Cadherin Clusters and actin filaments

钙粘蛋白簇和肌动蛋白丝

基本信息

批准号：
10579179
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
项目类别：
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/10579179
关键词：
Actins Adaptor Signaling Protein Adherens Junction Adhesions Adhesives Amaze Binding Binding Proteins Cadherins Cell Polarity Cell-Cell Adhesion Cells Complex Coupled Cytoskeletal Modeling Cytoskeleton Data Development Event F-Actin Foundations Generations Individual Lateral Link Liquid substance Mediating Medicine Microfilaments Molecular Morphogenesis Play Process Proliferating Proteins Radial Reaction Regulation Role Signal Pathway Signal Transduction Signaling Protein Stratification Structure Testing Time Tissues Vertebrates Work alpha catenin cell motility design experimental study extracellular flexibility fortification in vitro Model in vivo intercalation mutant nanocluster novel pharmacologic practical application recruit scaffold segregation solid state

Actins Adaptor Signaling Protein Adherens Junction Adhesions Adhesives Amaze Binding Binding Proteins Cadherins Cell Polarity Cell-Cell Adhesion Cells Complex Coupled Cytoskeletal Modeling Cytoskeleton Data Development Event F-Actin Foundations Generations Individual Lateral Link Liquid substance Mediating Medicine Microfilaments Molecular Morphogenesis Play Process Proliferating Proteins Radial Reaction Regulation Role Signal Pathway Signal Transduction Signaling Protein Stratification Structure Testing Time Tissues Vertebrates Work alpha catenin cell motility design experimental study extracellular flexibility fortification in vitro Model in vivo intercalation mutant nanocluster novel pharmacologic practical application recruit scaffold segregation solid state

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项目摘要

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.

钙粘蛋白聚类是介导和控制细胞粘合剂的独特分子过程。在此外，它还调节肌动蛋白细胞骨架，极性，增殖，显然是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 - 细胞粘合剂链接。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，它们为各种提供特定的结构支架信号通路。尽管功能非常重要，显然几乎可以发挥作用组织形态发生的各个方面，分子机制和钙粘蛋白的调节聚类仍有待研究。该建议将阐明钙粘蛋白簇的形成方式以及如何他们参与了如此的潜水细胞机制。往年在该提案中完成的工作表明，座椅连接（AJS）是主要的脊椎动物中的细胞细胞粘合剂结构，由许多瞬态但高度粘合剂组成 cadherin纳米簇。每个集群的短寿命使AJS粘合剂和柔性在相同的时间。这些簇的连续产生显然是基于一个显着的反应 - 钙粘着蛋白相关蛋白α-catenin与肌动蛋白丝的合作结合。大会 - cadherin簇和相关的F-肌动蛋白的分解循环紧密耦合在相邻细胞中同步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着蛋白/catenin结合的蛋白在结构上多样化。钙粘蛋白的多样化聚类基于以下事实：这些蛋白质中的每一种都提供了侧钙蛋白的特定模式钙粘蛋白相互作用。这些相互作用的各种相互作用导致形成一系列不同的簇每个都可能具有特定的功能。理解钙粘蛋白聚类的进步允许我们提出此建议，其中包括：（i）钙粘蛋白在聚类和两种蛋白质的功能，信号蛋白Erbin和衔接蛋白plekha5; （ii）分子与F-肌动蛋白的α-catenin结合互连的机制将细胞外钙粘蛋白结合事件相互连接；（iii）钙粘蛋白聚类在某些组织形态发生的例子中的作用。