Mechanisms of Formin-Mediated Actin Filament Assembly - Renewal 01 - Resubmission

福尔明介导的肌动蛋白丝组装机制 - 续订 01 - 重新提交

基本信息

  • 批准号:
    8985681
  • 负责人:
  • 金额:
    $ 38.66万
  • 依托单位:
  • 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 2017-12-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Cells simultaneously assemble functionally diverse actin cytoskeleton filaments with distinct architectures and dynamics to drive fundamental processes such as polarization, endocytosis, motility and division. Multiple actin filament-based structures must self-organize within a single crowded cytoplasm to maintain organization and functional specificity. Numerous actin-binding proteins with different properties regulate actin assembly and organization. Cells remain poised to assemble actin filaments at the right time and place in response to signals because they maintain a large pool of actin monomers bound to the small actin-binding protein profilin. Profilin prevents unwanted spontaneous actin assembly by inhibiting nucleation, so factors are required to rapidly stimulate actin assembly at the right time and place in response to signals. Most new actin filaments are produced by an expanding list of nucleation and elongation factors that establish diverse actin filament architectures required for different processes. Formin utilizes a conceptually novel mechanism to stimulate the assembly of rapidly elongating long-straight filaments that are often pulled by myosin motors to generate contractile forces or to provide polarized tracks and/or scaffolds that establish/maintain cell polarity and filopodia extension. Ena/VASP also promotes the elongation of long-straight filaments for extending filopodia at the leading edge of migrating cells. Conversely, Arp2/3 complex initiates the assembly of short-branched filaments that provide pushing forces. A major unresolved question is to determine how diverse nucleation factors work alone and in combination to assemble profilin-actin into functionally diverse actin filaments within a crowded common cytoplasm. Our hypothesis is that actin monomers are limiting, and therefore competition for profilin-actin by nucleation factors plays a critical role in maintaininga balance between different actin filament-based structures within a crowded cytoplasm. Profilin not only facilitates formin- and Ena/VASP-mediated actin filament elongation, but also allows formin to successfully compete with an excess of Arp2/3 complex for actin monomers. Our research goals are to determine the essential cellular role(s) of profilin, and follow up on progress made in our previous grant to investigate the precise mechanisms by which formins utilize profilin-actin for rapid actin filament elongation (Aim I). We are also expanding into the high impact area of investigating how formin competes with Arp2/3 complex for profilin-actin to drive different processes (Aim II), and how formin competes and/or cooperates with Ena/VASP to assemble actin filaments for filopodia (Aim III).
描述(申请人提供):细胞同时组装不同功能的肌动蛋白细胞骨架细丝,具有不同的结构和动力学,以驱动极化、内吞、运动和分裂等基本过程。多个基于肌动蛋白细丝的结构必须在一个拥挤的细胞质内自组织,以保持组织和功能的特异性。许多不同性质的肌动蛋白结合蛋白调节肌动蛋白的组装和组织。细胞仍然准备在正确的时间和地点组装肌动蛋白细丝,以响应信号,因为它们保持着大量的肌动蛋白单体与小的肌动蛋白结合蛋白Profilin结合。Profilin通过抑制核化来防止不必要的自发肌动蛋白组装,因此需要因子在正确的时间和地点快速刺激肌动蛋白组装以响应信号。大多数新的肌动蛋白细丝是由越来越多的成核和延长因素产生的,这些因素建立了不同过程所需的不同肌动蛋白细丝结构。Form in利用一种概念上新颖的机制来刺激快速伸长的长而直的细丝的组装,这些细丝通常由肌球蛋白马达拉动以产生收缩力量,或者提供建立/维持细胞极性和丝足延伸的极化轨道和/或支架。Ena/Vasp还促进长直细丝的伸长,以在迁移细胞的前缘延伸丝足。相反,Arp2/3复合体启动提供推动力的短分支细丝的组装。一个尚未解决的主要问题是确定不同的成核因素如何单独和联合作用,在拥挤的共同细胞质中将Profilin-Actin组装成功能不同的肌动蛋白细丝。我们的假设是,肌动蛋白单体是有限的,因此,成核因子对Profilin-肌动蛋白的竞争在维持拥挤细胞质中不同肌动蛋白细丝结构之间的平衡方面起着至关重要的作用。Profilin不仅促进Form in和EnA/Vasp介导的肌动蛋白细丝的延长,而且还允许Forin成功地与过量的Arp2/3复合体竞争肌动蛋白单体。我们的研究目标是确定Profilin的基本细胞角色(S),并跟进我们之前的拨款所取得的进展,以研究Forins利用Profilin-肌动蛋白快速延长肌动蛋白细丝的精确机制(目标I)。我们还在扩展到高影响领域,研究福尔明如何与Arp2/3复合体竞争Profilin-肌动蛋白以驱动不同的过程(Aim II),以及福尔明如何与Ena/Vasp竞争和/或合作组装肌动蛋白细丝以形成丝足(Aim III)。

项目成果

期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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David R Kovar其他文献

David R Kovar的其他文献

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{{ truncateString('David R Kovar', 18)}}的其他基金

Dynamic control of actin network architecture in early C. elegans embryos
早期秀丽隐杆线虫胚胎中肌动蛋白网络结构的动态控制
  • 批准号:
    10461861
  • 财政年份:
    2021
  • 资助金额:
    $ 38.66万
  • 项目类别:
Dynamic control of actin network architecture in early C. elegans embryos
早期秀丽隐杆线虫胚胎中肌动蛋白网络结构的动态控制
  • 批准号:
    10280989
  • 财政年份:
    2021
  • 资助金额:
    $ 38.66万
  • 项目类别:
Dynamic control of actin network architecture in early C. elegans embryos
早期秀丽隐杆线虫胚胎中肌动蛋白网络结构的动态控制
  • 批准号:
    10630246
  • 财政年份:
    2021
  • 资助金额:
    $ 38.66万
  • 项目类别:
Mechanisms of Formin-Mediated Actin Filament Assembly in Fission Yeast
裂殖酵母中福尔明介导的肌动蛋白丝组装机制
  • 批准号:
    8136522
  • 财政年份:
    2007
  • 资助金额:
    $ 38.66万
  • 项目类别:
Actin Cytoskeleton Network Self-Organization
肌动蛋白细胞骨架网络自组织
  • 批准号:
    10543764
  • 财政年份:
    2007
  • 资助金额:
    $ 38.66万
  • 项目类别:
Mechanisms of Formin-Mediated Actin Filament Assembly in Fission Yeast
裂殖酵母中福尔明介导的肌动蛋白丝组装机制
  • 批准号:
    7928718
  • 财政年份:
    2007
  • 资助金额:
    $ 38.66万
  • 项目类别:
Actin Cytoskeleton Network Self-Organization
肌动蛋白细胞骨架网络自组织
  • 批准号:
    10319960
  • 财政年份:
    2007
  • 资助金额:
    $ 38.66万
  • 项目类别:
Mechanisms of Formin-Mediated Actin Filament Assembly in Fission Yeast
裂殖酵母中福尔明介导的肌动蛋白丝组装机制
  • 批准号:
    7318798
  • 财政年份:
    2007
  • 资助金额:
    $ 38.66万
  • 项目类别:
Mechanisms of Formin-Mediated Actin Filament Assembly in Fission Yeast
裂殖酵母中福尔明介导的肌动蛋白丝组装机制
  • 批准号:
    7482445
  • 财政年份:
    2007
  • 资助金额:
    $ 38.66万
  • 项目类别:
Actin Cytoskeleton Network Self-Organization
肌动蛋白细胞骨架网络自组织
  • 批准号:
    10083213
  • 财政年份:
    2007
  • 资助金额:
    $ 38.66万
  • 项目类别:

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A novel motility system driven by two classes of bacterial actins MreB
由两类细菌肌动蛋白 MreB 驱动的新型运动系统
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多种植物肌动蛋白的差异表达
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研究肌动蛋白和微管如何协调及其相关性。
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  • 财政年份:
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拟南芥生殖肌动蛋白的抑制
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    6546977
  • 财政年份:
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拟南芥生殖肌动蛋白的抑制
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肌动蛋白和肌动蛋白结合蛋白的结构/相互作用
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