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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.

钙粘附素黏附的显著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性组织重塑。这个项目的长期目标是定义如何基于钙粘素粘附力结合了使细胞保持在一起的强度和允许快速细胞-细胞接触的重组。我们的最新结果，在这项提案中概述，提出了一种新的概念模型结合部组装和运行。我们提出了强有力的证据表明，钙粘素相关蛋白α-连接素与肌动蛋白细丝的连接持续产生钙粘素簇由细胞膜上的数百个分子组成。这些产品的主要特点是星团的存在是短暂的，并不一定会发生相互作用。同时随着时间的推移，它们具有高度的粘附性，因为它们的粘附性界面被细胞内的肌动蛋白加强了脚手架。我们认为，这种短暂但高度粘合的星团可能是粘着连接的可塑性，允许细胞在形态发生过程中重新调整它们的连接。我们的初步数据显示，这些星系团、它们的形成、动力学和结构特征可以使用先进的成像技术进行研究，如TIRF显微镜、散斑荧光显微镜、单分子定位显微镜和铂复制电子显微镜。在……里面结合生物物理测量和点突变，我们将确定肌动蛋白是如何细丝使用这些高度粘连的钙粘附素簇来管理细胞间的粘连。