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:
- 金额:$ 37.61万
- 依托单位:
- 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:
- 关键词:ActinsAddressAdherens JunctionAdhesionsAdhesivesAffectAffinityAntibodiesAtopic DermatitisAutoantibodiesBindingCadherinsCell AdhesionCell membraneCell-Cell AdhesionCellsCharacteristicsColorComplexCytoskeletonDNA Sequence AlterationDataDefectDesmosomesDevelopmentDiseaseElectron MicroscopyEpidermisFilamentGoalsHumanImageImaging TechniquesInterventionLifeLiquid substanceMaintenanceMediatingMedicineMicrofilamentsMicroscopyModelingMolecularMolecular ModelsMorphogenesisMutagenesisPhysiologicalPlatinumProcessPropertyProteinsPsoriasisReactionRegulationRoleRouteSiteSkinStructureTestingTimeTissuesTotal Internal Reflection FluorescentToxinWorkXenopusalpha cateninbasebiophysical propertiescarcinogenesiscell motilitycrosslinkextracellularflexibilitykeratinocytemolecular modelingmutantnanosizednovelnovel therapeuticspolymerizationpractical applicationresearch studyscaffoldsingle moleculeskin organogenesissolid 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。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Sergey M Troyanovsky其他文献
Sergey M Troyanovsky的其他文献
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{{ truncateString('Sergey M Troyanovsky', 18)}}的其他基金
Functional and Structural Links between Cadherin, Gamma-Secretase, and Notch
钙粘蛋白、γ-分泌酶和 Notch 之间的功能和结构联系
- 批准号:
8654254 - 财政年份:2010
- 资助金额:
$ 37.61万 - 项目类别:
Functional and Structural Links between Cadherin, Gamma-Secretase, and Notch
钙粘蛋白、γ-分泌酶和 Notch 之间的功能和结构联系
- 批准号:
8271257 - 财政年份:2010
- 资助金额:
$ 37.61万 - 项目类别:
Functional and Structural Links between Cadherin, Gamma-Secretase, and Notch
钙粘蛋白、γ-分泌酶和 Notch 之间的功能和结构联系
- 批准号:
8469391 - 财政年份:2010
- 资助金额:
$ 37.61万 - 项目类别:
Functional and Structural Links between Cadherin, Gamma-Secretase, and Notch
钙粘蛋白、γ-分泌酶和 Notch 之间的功能和结构联系
- 批准号:
8111101 - 财政年份:2010
- 资助金额:
$ 37.61万 - 项目类别:
Functional and Structural Links between Cadherin, Gamma-Secretase, and Notch
钙粘蛋白、γ-分泌酶和 Notch 之间的功能和结构联系
- 批准号:
7987304 - 财政年份:2010
- 资助金额:
$ 37.61万 - 项目类别:
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