An Izumo-Like Protein in C. elegans and its Role during Fertilization

线虫中的出云样蛋白及其在受精过程中的作用

基本信息

  • 批准号:
    8207961
  • 负责人:
  • 金额:
    $ 19.38万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2011
  • 资助国家:
    美国
  • 起止时间:
    2011-01-01 至 2013-12-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Fertilization requires that two dissimilar cells fuse their plasma membranes to create a zygote. This process is poorly understood and there has been no evidence it is well-conserved. We recently discovered C. elegans Izumo-like (CEIZUMO), which is the first case of a homologous membrane protein required for fertilization in both mammals and nematodes. Under specific aim 1, we will identify the location and role of CeIzumo during fertilization in vivo. Our studies will first use immunological approaches to characterize and visualize C. elegans CEIZUMO. This is will determine where CEIZUMO is localized to facilitate cell-cell fusion and reveal other features it might share with other well-characterized C. elegans and mouse fertilization mutants. We will use a transgenic approach to determine which parts of CeIzumo and worm/mouse gene chimeras restore self-fertility to the CeIzumo mutant; we already know that the mouse Ig domain can be swapped into CeIzumo without compromising its function. Under specific aim 2, we will determine if CeIzumo is a C. elegans sperm fusogen in vitro. We will develop an in vitro fertilization system to allow determination of the precise point where CEIZUMO acts. We will also establish whether an extracellular fragment of CEIZUMO can bind to unfertilized eggs. If successful, this will be followed by an RNAi screen for egg surface CEIZUMO receptors. The emerging picture is that worm and mammalian Izumo homologs are orthologous and could define a "core" cell-cell fusion mechanism that has been conserved during fertilization in animals. Antibodies to Izumo are known to block human sperm-egg fusion, suggesting that this protein is an outstanding contraceptive target. The C. elegans experiments described in this proposal already suggest that a high throughput assay for small molecules that block human Izumo function might be possible. PUBLIC HEALTH RELEVANCE: Fertilization is a process with significant public health implications because ~15% of couples desiring children are infertile and many cases are due to defective sperm. We have discovered that cell-cell-fusion during fertilization in nematodes may be similar to that which occurs in humans. We will exploit the significant experimental advantages offered by nematodes for analyzing this important problem in reproductive biology.
描述(由申请人提供):受精需要两个不同的细胞融合它们的质膜以产生受精卵。这一过程知之甚少,也没有证据表明它是保存完好的。我们最近发现了C。elegans Izumo-like(CEIZUMO),这是哺乳动物和线虫中受精所需的同源膜蛋白的第一例。在具体目标1下,我们将确定CeIzumo在体内受精过程中的位置和作用。我们的研究将首先使用免疫学方法来表征和可视化C。[医]秀丽隐翅虫这将确定CEIZUMO的定位,以促进细胞-细胞融合,并揭示它可能与其他特征良好的C。线虫和小鼠受精突变体。我们将使用转基因方法来确定CeIzumo和蠕虫/小鼠基因嵌合体的哪些部分恢复CeIzumo突变体的自育性;我们已经知道,小鼠IG结构域可以交换到CeIzumo而不损害其功能。在具体目标2下,我们将确定CeIzumo是否为C。线虫精子体外融合剂。我们将开发一种体外受精系统,以确定CEIZUMO作用的精确点。我们还将确定CEIZUMO的细胞外片段是否可以与未受精卵结合。如果成功,这将是随后的RNA干扰筛选鸡蛋表面CEIZUMO受体。新出现的图片是,蠕虫和哺乳动物出云同源物是orthopathic,并可以定义一个“核心”细胞融合机制,已在动物受精过程中保存。已知Izumo的抗体可以阻断人类精卵融合,这表明这种蛋白质是一种出色的避孕靶点。梭在该提议中描述的elegans实验已经表明阻断人Izumo功能的小分子的高通量测定是可能的。 公共卫生相关性:受精是一个具有重大公共卫生意义的过程,因为约15%的渴望孩子的夫妇是不育的,许多情况是由于精子缺陷。我们发现线虫受精过程中的细胞-细胞融合可能与人类相似。我们将利用线虫提供的重要实验优势来分析生殖生物学中的这一重要问题。

项目成果

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STEVEN W. L'HERNAULT其他文献

STEVEN W. L'HERNAULT的其他文献

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{{ truncateString('STEVEN W. L'HERNAULT', 18)}}的其他基金

An Izumo-Like Protein in C. elegans and its Role during Fertilization
线虫中的出云样蛋白及其在受精过程中的作用
  • 批准号:
    8064601
  • 财政年份:
    2011
  • 资助金额:
    $ 19.38万
  • 项目类别:
Secretory Vesicle Function During Spermatogenesis & Fertilization in C. elegans
精子发生过程中的分泌囊泡功能
  • 批准号:
    7349913
  • 财政年份:
    2007
  • 资助金额:
    $ 19.38万
  • 项目类别:
Secretory Vesicle Function During Spermatogenesis & Fertilization in C. elegans
精子发生过程中的分泌囊泡功能
  • 批准号:
    7495134
  • 财政年份:
    2007
  • 资助金额:
    $ 19.38万
  • 项目类别:
Secretory Vesicle Function During Spermatogenesis & Fertilization in C. elegans
精子发生过程中的分泌囊泡功能
  • 批准号:
    7673933
  • 财政年份:
    2007
  • 资助金额:
    $ 19.38万
  • 项目类别:
Secretory Vesicle Function During Spermatogenesis & Fertilization in C. elegans
精子发生过程中的分泌囊泡功能
  • 批准号:
    7920958
  • 财政年份:
    2007
  • 资助金额:
    $ 19.38万
  • 项目类别:
GENETICS OF CAENORHABDITIS ELEGANS SPERM MORPHOGENESIS
秀丽隐杆线虫精子形态发生的遗传学
  • 批准号:
    2022249
  • 财政年份:
    1988
  • 资助金额:
    $ 19.38万
  • 项目类别:
GENETICS OF CAENORHABDITIS ELEGANS SPERM MORPHOGENESIS
秀丽隐杆线虫精子形态发生的遗传学
  • 批准号:
    2608882
  • 财政年份:
    1988
  • 资助金额:
    $ 19.38万
  • 项目类别:
GENETICS OF CAENORHABDITIS ELEGANS SPERM MORPHOGENESIS
秀丽隐杆线虫精子形态发生的遗传学
  • 批准号:
    6053522
  • 财政年份:
    1988
  • 资助金额:
    $ 19.38万
  • 项目类别:
GENETICS OF CAENORHABIDITIS ELEGANS SPERM MORPHOGENESIS
秀丽隐杆线虫精子形态发生的遗传学
  • 批准号:
    3467284
  • 财政年份:
    1988
  • 资助金额:
    $ 19.38万
  • 项目类别:
GENETICS OF CAENORHABIDITIS ELEGANS SPERM MORPHOGENESIS
秀丽隐杆线虫精子形态发生的遗传学
  • 批准号:
    3467287
  • 财政年份:
    1988
  • 资助金额:
    $ 19.38万
  • 项目类别:

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