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Actin Cytoskeleton Network Self-Organization

肌动蛋白细胞骨架网络自组织

基本信息

批准号：
10543764
负责人：
David R Kovar
金额：
$ 40.94万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-01 至 2024-12-31
项目状态：
已结题

项目摘要

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/总结细胞组装功能多样的肌动蛋白细胞骨架网络，具有不同的结构和驱动极化、内吞作用、运动和分裂等基本过程的动力学。这不同肌动蛋白丝网络的具体特征（肌动蛋白丝密度、组织和动力学）是通过特定肌动蛋白结合蛋白组的协调作用来确定的（ABP）具有互补的结合特性。大多数研究主要集中于单个 F-肌动蛋白网络。然而，这对 F-肌动蛋白网络组织和因为细胞通常在细胞内同时组装和使用多个 F-肌动蛋白网络相同的细胞质。因此，F-肌动蛋白网络必须从共享的公共池中自组织肌动蛋白单体和重叠的 ABP 组。我们预测有重要的相互作用对其形式和功能至关重要的网络之间的（串扰）。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，这至关重要用于在共同的细胞质内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调节的机制竞争有限量的肌动蛋白单体（目标 I）。尽管未组装的 G-肌动蛋白并未尽管被认为是有限的，但我们系统地证明了 G-肌动蛋白的竞争有助于控制大小和裂殖酵母中竞争性 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-肌动蛋白的竞争中发挥重要作用。我们的目标是确定底层 Profilin 和其他 ABP 有助于 G-肌动蛋白在细胞间正确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得一组特定的 ABP，其互补的生化活动有助于定义它们形式和功能（目标 II）。我们将研究潜在的内在分子机制 ABP 自分类到共同细胞质内的特定 F-肌动蛋白网络，包括 (1) ABP 之间与肌动蛋白丝结合的竞争和合作，以及 (2) 肌动蛋白是否组装因子通过偏向特定 ABP 的关联来启动自排序。