Coordination of the actin and microtubule cytoskeletons

肌动蛋白和微管细胞骨架的协调

• 批准号: 8613495
• 负责人: JEFF GELLES
• 金额: $ 32.27万
• 依托单位: BRANDEIS UNIVERSITY
• 依托单位国家: 美国
• 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/8613495
• 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

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）：本研究的目的是确定肌动蛋白和微管细胞骨架的动力学如何通过一组三种相互作用的哺乳动物蛋白：APC， Dia1和EB1进行协调。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的活性和相互作用的更深层次的理解。本项目采用大量生化实验结合一种新颖的多波长单分子生物物理学方法，旨在阐明体外复杂的多组分调控系统的机制。此外，从体外实验中推断出的机制将在体内进行测试，以验证它们对这些蛋白质在活细胞中的相关生物学功能（例如，定向细胞迁移）的重要性。具体目的是：(1)验证关于Dia1和APC协同促进肌动蛋白组装机制的两个关键假设，包括组分之间形成拟议的物理复合物；(2)验证了Dia1和APC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。