Actin Cytoskeleton Network Self-Organization

肌动蛋白细胞骨架网络自组织

• 批准号: 9887915
• 负责人: David R Kovar
• 金额: $ 43.88万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9887915
• 关键词: Actin-Binding Protein; Actins; Address; Architecture; Behavior; Behavioral Mechanisms; Binding; Biochemical; Biological; Biological Assay; Cells; Characteristics; Collection; Color; Complex; Cytoplasm; Cytoskeleton; Development; Disease; Endocytosis; Excision; F-Actin; Feedback; Fimbrin; Fission Yeast; Funding; G Actin; Goals; Image; In Vitro; Individual; Investigation; Mediating; Microfilaments; Molecular; Play; Process; Property; Protein Isoforms; Protein Sortings; Proteins; Role; Shapes; Sorting - Cell Movement; Surveys; Testing; Total Internal Reflection Fluorescent; Tropomyosin; Work; alpha Actinin; cell motility; cofilin; density; genetic regulatory protein; imaging approach; monomer; mutant; profilin; reconstitution; self organization; single molecule

PROJECT ABSTRACT/SUMMARY Cells assemble functionally diverse actin cytoskeleton networks with distinct architectures and dynamics to drive fundamental processes such as polarization, endocytosis, motility and division. The specific characteristics of different actin filament networks (actin filament density, organization and dynamics) are determined through the coordination action of specific sets of actin binding proteins (ABPs) with complementary binding properties. Most investigations primarily focus on individual F-actin networks. However, this provides limited overall understanding of F-actin network organization and function because cells typically assemble and use multiple F-actin networks simultaneously within the same cytoplasm. Consequently, F-actin networks must self-organize from a common pool of shared actin monomers and overlapping sets of ABPs. We have predicted that there are important interactions (cross talk) between networks that are critical for their form and function. Our long-term goal is to discover the direct and indirect interactions between self-organized F-actin networks, which are critical for establishing their unique identities and functions within a common cytoplasm, and to determine the underlying molecular mechanistic principles that govern these interactions. We are investigating two major actin cytoskeleton self-organization questions. The first is to determine the mechanisms by which the size and density of F-actin networks are regulated by competition for a limiting amount of actin monomers (Aim I). Although unassembled G-actin was not thought to be limiting, we systematically showed that competition for G-actin helps control the size and density of competitive F-actin networks in fission yeast, and that the actin monomer protein profilin plays a major role in regulating competition for limiting G-actin. Our goal is to determine the underlying mechanism by which profilin and other ABPs contribute to the proper distribution of G-actin between functionally diverse actin cytoskeleton networks. The second is to determine how diverse F-actin networks acquire the specific set of ABPs whose complementary biochemical activities help define their form and function (Aim II). We will investigate the underlying intrinsic molecular mechanisms by which ABPs self-sort to particular F-actin networks within a common cytoplasm, including (1) the contribution of competition and cooperation between ABPs for associating with actin filaments, and (2) whether actin assembly factors initiate self-sorting by biasing the association of particular ABPs.

项目摘要/摘要 细胞在功能上多样化的肌动蛋白细胞骨架网络具有不同的架构，并且 驱动基本过程的动力学，例如极化，内吞作用，运动和分裂。这 不同肌动蛋白细丝网络（肌动蛋白丝密度，组织和 动力学）是通过特定的肌动蛋白结合蛋白的协调作用来确定的 （ABP）具有互补结合特性。大多数调查主要关注单个F-肌动蛋白 网络。但是，这提供了对F-肌动蛋白网络组织和 功能是因为单元格通常在 相同的细胞质。因此，F-肌动蛋白网络必须从共享的共同池中自组织 肌动蛋白单体和ABP的重叠集。我们已经预测存在重要的互动 （串联）在网络之间对其形式和功能至关重要的网络之间。我们的长期目标是 发现自组织的F-肌动蛋白网络之间的直接和间接相互作用，这是关键的 在共同的细胞质中建立其独特的身份和功能，并确定 控制这些相互作用的基本分子机械原理。 我们正在研究两个主要的肌动蛋白细胞骨架自组织问题。首先是 确定F-肌动蛋白网络的大小和密度受到调节的机制 竞争限制肌动蛋白单体数量的竞争（AIM I）。虽然未组装的g-肌动蛋白不是 被认为是限制的，我们系统地表明，G-肌动蛋白的竞争有助于控制大小和 裂变酵母中竞争性F-肌动蛋白网络的密度，而肌动蛋白单体蛋白胶原蛋白发挥 在规范限制G-肌动蛋白的竞争方面起着主要作用。我们的目标是确定基础 profilin和其他ABP促进G-肌动蛋白适当分布的机制 功能多样的肌动蛋白细胞骨架网络。第二个是确定f-肌动蛋白的多样化 网络获得了特定的ABP，其互补的生化活动有助于定义其 形式和功能（AIM II）。我们将研究潜在的固有分子机制 ABP自我分类到普通细胞质内的特定F-肌动蛋白网络，包括（1） ABP与肌动蛋白丝之间的竞争与合作，以及（2）肌动蛋白是否存在 组装因子通过偏向特定ABP的关联来启动自我分类。