Regulation of nuclear migration

核迁移的监管

基本信息

  • 批准号:
    6919268
  • 负责人:
  • 金额:
    $ 28.07万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2004
  • 资助国家:
    美国
  • 起止时间:
    2004-08-01 至 2008-07-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): The nucleus of the typical eukaryotic cell is located at a defined region and maintained there through active processes. Consequently changes in nuclear position are often highly regulated and play important developmental and cellular roles. Despite the ubiquity of nuclear migration, relatively little is known about the genetics and cell biology of this process in higher eukaryotes. The long-term objective of this research is to determine the mechanisms underlying nuclear migration and to understand its regulation during development, using Drosophila as a model system. Nuclear migration involves an evolutionarily conserved pathway that acts through the microtubule motor cytoplasmic dynein. The Drosophila nudC (DnudC) and Drosophila Lisl (DLisl) genes have important regulatory roles in this process and dynein is essential for movement and anchoring of the oocyte nucleus. We propose to study the mechanism by which dynein function is regulated by genes in the nuclear migration pathway using molecular and biochemical approaches. These studies will provide significant insights into how nuclear migration is regulated in a higher eukaryote and help in understanding how the activity and specificity of dynein, a key microtubule dependent motor can be modulated. Mutations in human LIS1 result in failure of neuronal migration during embryogenesis causing severe mental retardation and premature death. In addition, missense mutations in dynein motor components cause human motor neuron disease and progressive motor neuron degeneration, underscoring the clinical relevance of determining how these ubiquitous motor complexes are regulated. The three specific aims of this proposal are: 1. To investigate the role of DLisl in regulating dynein motor activity: We will examine how DLisl affects dynein function using molecular, genetic and biochemical approaches as well as a sensitive assay that directly measures motor activity in vivo. 2. To determine the biological function of DnudC: We will investigate the role of DnudC, a potential regulator of DLisl and carry out a phenotypic analysis of mutants we have isolated in DnudC. 3. To understand the mechanistic basis of DnudC function: Genetic and structure/function analysis will be used to examine regulatory interactions between DLisl/DnudC and the mechanistic basis of DnudC action.
描述(由申请人提供):典型真核细胞的细胞核位于指定区域并通过活跃过程维持在那里。因此,核位置的变化通常受到高度调控,并发挥重要的发育和细胞作用。尽管核迁移无处不在,但人们对高等真核生物中这一过程的遗传学和细胞生物学知之甚少。这项研究的长期目标是使用果蝇作为模型系统,确定核迁移的机制并了解其在发育过程中的调节。核迁移涉及通过微管运动细胞质动力蛋白起作用的进化保守途径。果蝇 nudC (DnudC) 和果蝇 Lisl (DLisl) 基因在此过程中具有重要的调节作用,动力蛋白对于卵母细胞核的运动和锚定至关重要。我们建议使用分子和生化方法研究核迁移途径中的基因调节动力蛋白功能的机制。这些研究将为如何在高等真核生物中调节核迁移提供重要的见解,并有助于理解如何调节动力蛋白(一种关键的微管依赖性马达)的活性和特异性。人类 LIS1 突变导致胚胎发生过程中神经元迁移失败,导致严重智力低下和过早死亡。此外,动力蛋白运动成分的错义突变会导致人类运动神经元疾病和进行性运动神经元变性,强调了确定这些普遍存在的运动复合体如何调节的临床相关性。该提案的三个具体目标是: 1. 研究 DLisl 在调节动力蛋白运动活动中的作用:我们将使用分子、遗传和生化方法以及直接测量体内运动活动的灵敏测定来研究 DLisl 如何影响动力蛋白功能。 2.确定DnudC的生物学功能:我们将研究DnudC(DLisl的潜在调节剂)的作用,并对我们在DnudC中分离的突变体进行表型分析。 3. 了解 DnudC 功能的机制基础:将使用遗传和结构/功能分析来检查 DLisl/DnudC 之间的调节相互作用和 DnudC 作用的机制基础。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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RAHUL WARRIOR其他文献

RAHUL WARRIOR的其他文献

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{{ truncateString('RAHUL WARRIOR', 18)}}的其他基金

Interplay of heavy metal homeostasis and cell growth-related signaling networks
重金属稳态和细胞生长相关信号网络的相互作用
  • 批准号:
    10431618
  • 财政年份:
    2022
  • 资助金额:
    $ 28.07万
  • 项目类别:
Interplay of heavy metal homeostasis and cell growth-related signaling networks
重金属稳态与细胞生长相关信号网络的相互作用
  • 批准号:
    10676781
  • 财政年份:
    2022
  • 资助金额:
    $ 28.07万
  • 项目类别:
Zeiss LSM 980 NLO Confocal Microscope with Airyscan2 for UCI Optical Biology Core
适用于 UCI 光学生物学核心的配备 Airyscan2 的 Zeiss LSM 980 NLO 共焦显微镜
  • 批准号:
    10429736
  • 财政年份:
    2022
  • 资助金额:
    $ 28.07万
  • 项目类别:
Regulation of nuclear migration
核迁移的监管
  • 批准号:
    6809778
  • 财政年份:
    2004
  • 资助金额:
    $ 28.07万
  • 项目类别:
Regulation of nuclear migration
核迁移的监管
  • 批准号:
    7101791
  • 财政年份:
    2004
  • 资助金额:
    $ 28.07万
  • 项目类别:
Regulation of nuclear migration
核迁移的监管
  • 批准号:
    7267591
  • 财政年份:
    2004
  • 资助金额:
    $ 28.07万
  • 项目类别:
GERM CELL MIGRATION IN DROSOPHILA
果蝇生殖细胞迁移
  • 批准号:
    2186164
  • 财政年份:
    1993
  • 资助金额:
    $ 28.07万
  • 项目类别:
GERM CELL MIGRATION IN DROSOPHILA
果蝇生殖细胞迁移
  • 批准号:
    3308141
  • 财政年份:
    1993
  • 资助金额:
    $ 28.07万
  • 项目类别:
GERM CELL MIGRATION IN DROSOPHILA
果蝇生殖细胞迁移
  • 批准号:
    2186165
  • 财政年份:
    1993
  • 资助金额:
    $ 28.07万
  • 项目类别:
GERM CELL MIGRATION IN DROSOPHILA
果蝇生殖细胞迁移
  • 批准号:
    2459473
  • 财政年份:
    1993
  • 资助金额:
    $ 28.07万
  • 项目类别:
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