Coordination of the actin and microtubule cytoskeletons

肌动蛋白和微管细胞骨架的协调

基本信息

批准号：
8454423
负责人：
JEFF GELLES
金额：
$ 31.14万
依托单位：
BRANDEIS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-05-01 至 2016-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8454423
关键词：
Actins Acute Lymphocytic Leukemia Adenomatous Polyposis Coli Adenomatous Polyposis Coli Protein Area Automobile Driving Behavior Binding Binding Proteins Binding Sites Biochemical Biochemistry Biological Biological Process Biophysics Cancer Etiology Cell Shape Cell physiology Cells Cellular Morphology Cellular biology Cessation of life Characteristics Colorectal Cancer Complex Cytoskeleton Defect Development Filament Fluorescence G Actin Gap Junctions Gene Fusion Genes Genetic Goals Grant Human In Vitro Individual Inherited Investigation Lead Life Link MLL gene Malignant Neoplasms Mediating Medical Methods Microfilaments Microscopy Microtubules Molecular Morphogenesis Mutation Pathway interactions Polymers Positioning Attribute Process Proteins Regulation Regulatory Pathway Research Research Personnel System Techniques Testing Triad Acrylic Resin Tumor Suppressor Proteins Ursidae Family Work biological systems cell growth regulation cell motility experience in vivo insight light microscopy novel polymerization protein complex research study single molecule tumorigenesis

项目摘要

DESCRIPTION (provided by applicant): The goal of this research is to determine how the dynamics of the actin and microtubule cytoskeletons are coordinated by a group of three interacting mammalian proteins: APC, Dia1, and EB1. This work will define the functions and mechanisms of these proteins, and provide a deeper understanding of the activities and interactions that underlie such processes as cell migration and morphogenesis. This project uses bulk biochemical experiments combined with a novel multi-wavelength single molecule biophysics method tailored to elucidate the mechanisms of complex, multi-component regulatory systems in vitro. In addition, the mechanisms deduced from the experiments in vitro will be tested in vivo to verify that they are important for relevant biological functions of these proteins in living cells (e.g., directed cell migration). The Specific Aims are: (1) Test two key hypotheses about the mechanism by which Dia1 and APC synergize in promoting actin assembly, involving formation of proposed physical complexes among components; (2) Test the additional hypothesis that Dia1 and APC synergize to stimulate actin assembly by a "rocket launcher" mechanism; and (3) Define the mechanisms by which EB1 alone and EB1 plus microtubules regulate and/or organize APC/Dia-induced actin assembly.

描述（由申请人提供）：本研究的目标是确定肌动蛋白和微管细胞骨架的动力学如何由一组三种相互作用的哺乳动物蛋白（APC、Dia1 和 EB1）协调。这项工作将定义这些蛋白质的功能和机制，并提供对细胞迁移和形态发生等过程背后的活动和相互作用的更深入的理解。该项目采用大量生化实验与新型多波长单分子生物物理学方法相结合，旨在阐明体外复杂的多组分调节系统的机制。此外，从体外实验推导出来的机制将在体内进行测试，以验证它们对于活细胞中这些蛋白质的相关生物学功能（例如定向细胞迁移）很重要。具体目标是：（1）测试关于 Dia1 和 APC 协同促进肌动蛋白组装的机制的两个关键假设，涉及成分之间形成所提出的物理复合物；（2）测试Dia1和APC通过“火箭发射器”机制协同刺激肌动蛋白组装的附加假设； (3) 明确 EB1 单独和 EB1 加微管调节和/或组织 APC/Dia 诱导的肌动蛋白组装的机制。