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(由申请人提供):细胞同时组装具有不同结构和动力学的功能多样的肌动蛋白细胞骨架丝,以驱动基本过程,如极化、内吞、运动和分裂。多个基于肌动蛋白的结构必须在单个拥挤的细胞质中自组织以保持组织和功能特异性。许多具有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。细胞在正确的时间和地点对信号做出反应,保持组装肌动蛋白丝的状态,因为它们保持了大量的肌动蛋白单体与小肌动蛋白结合蛋白profilin结合。Profilin通过抑制成核来防止不需要的自发肌动蛋白组装,因此需要因子来响应信号在正确的时间和地点快速刺激肌动蛋白组装。大多数新的肌动蛋白丝是由不断扩大的成核和延伸因子产生的,这些因子建立了不同过程所需的不同肌动蛋白丝结构。形成蛋白利用一种概念上新颖的机制来刺激快速伸长的长直细丝的组装,这些细丝通常由肌球蛋白马达拉动以产生收缩力或提供建立/维持细胞极性和丝状伪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状伪足。相反,Arp 2/3复合物启动提供推力的短分支细丝的组装。一个主要的未解决的问题是,以确定不同的成核因子如何单独和组合组装成功能不同的肌动蛋白微丝在一个拥挤的共同细胞质内的profilin-actin。 我们的假设是,肌动蛋白单体是有限的,因此竞争的profilin-actin的成核因子中起着至关重要的作用,在一个拥挤的细胞质中,不同的肌动蛋白的免疫力为基础的结构之间的平衡。Profilin不仅促进β-和Ena/VASP介导的肌动蛋白丝伸长,而且还允许β-与过量的Arp 2/3复合物成功地竞争肌动蛋白单体。我们的研究目标是确定profilin的基本细胞作用,并跟进我们以前的资助所取得的进展,以调查formin利用profilin-actin快速肌动蛋白丝伸长的确切机制(Aim I)。我们还扩展到高影响力的领域,研究ENA如何与Arp 2/3复合物竞争profilin-actin以驱动不同的过程(Aim II),以及ENA如何与ENA/VASP竞争和/或合作以组装丝状伪足的肌动蛋白丝(Aim III)。

项目成果

期刊论文数量(0)
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会议论文数量(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:
    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:
    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:
    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:
    9887915
  • 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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    7931495
  • 财政年份:
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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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    19390048
  • 财政年份:
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拟南芥生殖肌动蛋白的抑制
  • 批准号:
    6655612
  • 财政年份:
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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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