Cadherin clusters and actin filaments

钙粘蛋白簇和肌动蛋白丝

基本信息

批准号：
9155342
负责人：
Sergey M Troyanovsky
金额：
$ 37.61万
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 2021-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9155342
关键词：
Actins Address Adherens Junction Adhesions Adhesives Affect Affinity Antibodies Atopic Dermatitis Autoantibodies Binding Cadherins Cell Adhesion Cell membrane Cell-Cell Adhesion Cells Characteristics Color Complex Cytoskeleton DNA Sequence Alteration Data Defect Desmosomes Development Disease Electron Microscopy Epidermis Filament Goals Human Image Imaging Techniques Intervention Life Liquid substance Maintenance Mediating Medicine Microfilaments Microscopy Modeling Molecular Molecular Models Morphogenesis Mutagenesis Physiological Platinum Process Property Proteins Psoriasis Reaction Regulation Role Route Site Skin Structure Testing Time Tissues Total Internal Reflection Fluorescent Toxin Work Xenopus alpha catenin base biophysical properties carcinogenesis cell motility crosslink extracellular flexibility keratinocyte molecular modeling mutant nanosized novel novel therapeutics polymerization practical application research study scaffold single molecule skin organogenesis solid state

项目摘要

One of the remarkable features of cadherin adhesion is its plasticity. This feature is crucial in normal and pathological tissue remodeling. The long-term goal of this project is to define how cadherin-based adhesion combines the strength that keeps cells together with the plasticity that allows for the fast restructuring of cell-cell contacts. Our recent results, outlined in this proposal, suggested a conceptually new model of adherens junction assembly and functioning. We present strong evidence that the cooperative binding of the cadherin-associated protein α-catenin to actin filaments continuously generates cadherin clusters consisting of hundreds of molecules on the cell plasma membrane. The major feature of these clusters is that they are short-lived and are not necessarily engaged in trans-interactions. At the same time, they are highly adhesive because their adhesive interface is reinforced by the intracellular actin scaffold. We propose that such transient, but highly adhesive clusters could be of the basis for the adherens junction plasticity, allowing cells to readjust their junctions during morphogenetic processes. Our preliminary data show that these clusters, their formation, dynamics, and structural characteristics can be studied using advanced imaging techniques such as TIRF microscopy, speckle fluorescent microscopy, single molecule localization microscopy, and platinum replica electron microscopy. In conjunction with biophysical measurements and point mutagenesis, we will determine how actin filaments use these highly adhesive cadherin clusters to manage intercellular adhesion.

钙粘蛋白粘附的显着特征之一是其可塑性。此功能在正常情况下至关重要和病理组织重塑。该项目的长期目标是定义基于钙粘蛋白的方式粘附结合了将细胞与可塑性保持在一起的强度细胞细胞接触的重组。我们最近在该提案中概述的结果提出了一个概念的新模型连接组件和功能。我们提供了有力的证据表明钙粘蛋白相关的蛋白α-catenin to肌动蛋白丝连续产生钙粘蛋白簇由细胞质膜上的数百个分子组成。这些的主要特征集群是它们是短暂的，不一定从事反互动。同样时间，它们具有很高的粘合剂，因为它们的粘合剂界面被细胞内肌动蛋白增强脚手架。我们建议这种短暂但高度粘合剂的簇可能是粘附的连接可塑性，使细胞在形态发生过程中可以重新调整其连接处。我们的初步数据表明，这些簇，它们的形成，动态和结构特征可以使用高级成像技术（例如TIRF显微镜，斑点荧光）进行研究显微镜，单分子定位显微镜和铂复制电子显微镜。在与生物物理测量和点诱变的联系，我们将确定肌动蛋白如何细丝使用这些高度粘附的钙粘蛋白簇来管理细胞间粘合剂。