Molecular mechanisms regulating local translation during axon growth and guidance

轴突生长和引导过程中调节局部翻译的分子机制

基本信息

  • 批准号:
    9171145
  • 负责人:
  • 金额:
    $ 37.5万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-07-01 至 2020-06-30
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY The long-term goal of this research is to understand the molecular mechanisms underlying the establishment of neuronal connectivity during development. Specifically, this research examines how the growth cone, which is the pathfinding structure of the developing neuron, migrates to and connects with its appropriate targets. Neuronal connectivity is directed via both external and internal cues, which results in the activation of various cellular signaling pathways and ultimately, cytoskeletal reorganization. This proposal focuses on understanding the molecular mechanisms linking cellular signaling and local translation in the developing nervous system. It has only recently been discovered that local translation in axonal growth cones is necessary for the processes of axon growth and guidance. As such, our understanding of local translation is very limited. This study focuses on a multifunctional scaffolding protein, RACK1, which likely provides a critical link between cellular signaling and the regulation of local translation. We have preliminary data that this local translation takes place at point contacts, which are adhesion sites within growth cones that are essential for appropriate axon growth and guidance. Thus, our preliminary data suggests that point contacts are not just adhesion sites, but also critical signaling centers. Here, we hypothesize that point contacts within growth cones serve as a strategic location for targeted local translation and RACK1 is critical to this process. This proposal will provide valuable research opportunities for both undergraduate and graduate students to study fundamental processes that take place during neural development. Using advanced live cell imaging, fluorescent translation reporters, shRNA and axon growth and guidance assays, here we will determine if local translation occurs at point contacts in growth cones, and examine how RACK1 regulates point contact dynamics and axon growth and guidance. Taken together, this research will enable a broad, mechanistic understanding as to how mRNA trafficking and local translation contributes to the establishment of neuronal connectivity, thereby increasing our knowledge about the complex nature of brain development.
项目摘要 这项研究的长期目标是了解建立这种机制的分子机制。 神经元的连接。具体来说,这项研究探讨了生长锥, 是发育中的神经元的寻路结构,迁移到适当的目标并与之连接。 神经元的连接是通过外部和内部线索来引导的,这导致各种神经元的激活。 细胞信号传导途径,并最终导致细胞骨架重组。这一建议的重点是了解 在发育中的神经系统中连接细胞信号和局部翻译的分子机制。它 最近才发现,轴突生长锥的局部平移对于这些过程是必要的 轴突的生长和引导。因此,我们对本地翻译的了解非常有限。本研究着重 多功能支架蛋白RACK1,它可能提供了细胞信号之间的关键联系, 以及当地翻译的规范。我们有初步的数据表明,这种本地翻译发生在点 接触,其是生长锥内的粘附位点,对于适当的轴突生长是必需的, 指导因此,我们的初步数据表明,点接触不仅是粘附部位, 信号中心在这里,我们假设生长锥内的点接触作为一个战略位置 对于有针对性的本地翻译,RACK1对此过程至关重要。这项建议将提供有价值的研究 本科生和研究生都有机会研究发生在他们身上的基本过程。 在神经发育过程中。使用先进的活细胞成像,荧光翻译报告,shRNA和 轴突生长和指导测定,在这里,我们将确定在生长中的点接触处是否发生局部翻译 视锥细胞,并研究RACK1如何调节点接触动力学和轴突生长和指导。采取 总之,这项研究将使人们能够广泛、机械地了解mRNA运输和局部表达的方式, 翻译有助于神经元连接的建立,从而增加了我们对 大脑发育的复杂性

项目成果

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Kristy Welshhans其他文献

Kristy Welshhans的其他文献

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{{ truncateString('Kristy Welshhans', 18)}}的其他基金

Regulating axon guidance through local translation at adhesions
通过粘连处的局部翻译调节轴突引导
  • 批准号:
    10587090
  • 财政年份:
    2023
  • 资助金额:
    $ 37.5万
  • 项目类别:
Regulating axon guidance through local translation at adhesions
通过粘连处的局部翻译调节轴突引导
  • 批准号:
    10841832
  • 财政年份:
    2023
  • 资助金额:
    $ 37.5万
  • 项目类别:
ZBP1-mediated transport and local translation of B-actin mRNA in growth cones
ZBP1 介导的生长锥中 B 肌动蛋白 mRNA 的运输和局部翻译
  • 批准号:
    8011057
  • 财政年份:
    2009
  • 资助金额:
    $ 37.5万
  • 项目类别:
ZBP1-mediated transport and local translation of B-actin mRNA in growth cones
ZBP1 介导的生长锥中 B 肌动蛋白 mRNA 的运输和局部翻译
  • 批准号:
    7759110
  • 财政年份:
    2009
  • 资助金额:
    $ 37.5万
  • 项目类别:
ZBP1-mediated transport and local translation of B-actin mRNA in growth cones
ZBP1 介导的生长锥中 B 肌动蛋白 mRNA 的运输和局部翻译
  • 批准号:
    7614650
  • 财政年份:
    2009
  • 资助金额:
    $ 37.5万
  • 项目类别:

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