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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/总结细胞组装具有不同结构的功能多样的肌动蛋白细胞骨架网络，动力学驱动基本过程，如极化，内吞作用，运动和分裂。的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）是通过特定的肌动蛋白结合蛋白的协调作用来确定的（ABPs）具有互补结合特性。大多数研究主要集中在单个F-肌动蛋白网络.然而，这提供了对F-肌动蛋白网络组织的有限的整体理解，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一个共享的共同池中自组织起来。肌动蛋白单体和ABP重叠组。我们已经预测到，（串扰）网络之间的形式和功能至关重要。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，这是至关重要的在一个共同的细胞质中建立它们独特的身份和功能，并确定它们的基因型。控制这些相互作用的潜在分子机械原理。我们正在研究两个主要的肌动蛋白细胞骨架自组织的问题。一是确定F-肌动蛋白网络的大小和密度受以下因素调节的机制：竞争有限数量的肌动蛋白单体（目的I）。虽然未组装的G-肌动蛋白被认为是限制，我们系统地表明，竞争G-肌动蛋白有助于控制大小，在分裂酵母中竞争性F-肌动蛋白网络的密度，以及肌动蛋白单体蛋白profilin发挥的作用，在限制G-肌动蛋白的竞争中起主要作用。我们的目标是确定 profilin和其他ABPs有助于G-肌动蛋白在细胞间的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-肌动蛋白网络获得一组特定的ABP，其互补的生化活动有助于定义其功能。形式和功能（目标二）。我们将研究潜在的内在分子机制， ABPs在一个共同的细胞质内自我分选到特定的F-肌动蛋白网络，包括（1） ABPs之间的竞争和合作与肌动蛋白丝，以及（2）是否肌动蛋白组装因子通过偏置特定ABP的缔合来启动自分选。