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 细胞组装功能多样的肌动蛋白细胞骨架网络，具有不同的结构和 推动极化、内吞、运动和分裂等基本过程的动力学。这个 不同肌动蛋白细丝网络的特定特征(肌动蛋白细丝密度、组织和 动力学)是通过特定的肌动蛋白结合蛋白集合的协调作用确定的 (ABPS)具有互补的结合特性。大多数研究主要集中在单个F-肌动蛋白上 网络。然而，这提供了对F-肌动蛋白网络组织和 功能，因为细胞通常同时组装并使用多个F-肌动蛋白网络 同样的细胞质。因此，F-肌动蛋白网络必须从公共的共享池中自组织 肌动蛋白单体和重叠的ABP集合。我们已经预测到有重要的相互作用 (串扰)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F-肌动蛋白网络之间的直接和间接相互作用，这是至关重要的 以确定它们在共同细胞质中的独特身份和功能，并确定 支配这些相互作用的潜在分子机制原理。 我们正在研究两个主要的肌动蛋白细胞骨架自组织问题。第一个是 确定F-肌动蛋白网络的大小和密度受 竞争有限数量的肌动蛋白单体(目标一)。尽管未组装的G-肌动蛋白不是 被认为是有限的，我们系统地证明了竞争G-肌动蛋白有助于控制大小和 分裂酵母中竞争性F-肌动蛋白网络的密度以及肌动蛋白单体蛋白Profilin的作用 在调节限制G-肌动蛋白的竞争中起主要作用。我们的目标是确定潜在的 Profilin和其他ABP促进G-肌动蛋白在G-肌动蛋白中适当分布的机制 功能多样的肌动蛋白细胞骨架网络。第二个是确定F-肌动蛋白的多样性 网络获取特定的一组ABP，其互补的生化活动有助于定义其 形式和功能(目标二)。我们将研究潜在的内在分子机制，通过它 ABPS对共同细胞质中特定的F-肌动蛋白网络进行自我排序，包括(1) ABPs与肌动蛋白细丝结合的竞争与合作；(2)肌动蛋白是否 装配因素通过偏向特定ABP的关联来启动自我排序。