Germ Granule Structure and Function in C. elegans

秀丽隐杆线虫的胚芽颗粒结构和功能

基本信息

批准号：
7845726
负责人：
Dustin Lynn Updike
金额：
$ 5.38万
依托单位：
UNIVERSITY OF CALIFORNIA SANTA CRUZ
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-06-01 至 2011-05-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Germ cells are the cells that give rise to the next generation of an organism. To perform this specialized task, germ cells must be totipotent and immortal. They acquire these characteristics by utilizing specialized regulatory mechanisms and factors, including germline-specific granules that overlie nuclear pores and are critical for germline development. Germ granules are cytoplasmic organelles that are conserved in germ cells from worms to mammals, and are associated with the immortal and totipotent properties of germ cells. To date, the mechanisms by which germ granules function are unknown. This proposal investigates the structure and function of germ granules in the model system C. elegans using a combination of genetic and biochemical approaches. The first aim tests whether a nuclear pore-like protein domain found within an already identified germ granule component interacts with and extends the nuclear pore environment. Nuclear pore proteins interact through this domain to form a permeability barrier between the cytoplasm and nucleus. Germ granule proteins that contain this nuclear pore-like domain will be tested to see if they interact with each other, and with nuclear pore associated components. In vivo tests will investigate these interactions in living cells. The second aim tests the hypothesis that germ granules create a microenvironment that can selectively exclude access to the nuclear pore and regulate nuclear import in the germ line. The third aim identifies new components required for proper germ granule assembly. I have already performed a genome-wide RNAi screen for such components. Classes of genes identified by this screen are beginning to reveal the mechanisms by which germ granules function. Most of these genes are conserved and so may inform us about germ granule functions across species. Our studies of germ cell biology in worms may contribute insights into regulatory mechanisms shared by germ cells, stem cells and cancer cells.

描述（由申请人提供）：生殖细胞是产生下一代生物体的细胞。为了执行这项专门的任务，生殖细胞必须是全能且永生的。它们通过利用专门的调节机制和因素来获得这些特征，包括覆盖核孔并对种系发育至关重要的种系特异性颗粒。生殖颗粒是从蠕虫到哺乳动物的生殖细胞中保守的细胞质细胞器，并且与生殖细胞的永生和全能特性相关。迄今为止，胚芽颗粒发挥作用的机制尚不清楚。该提案结合遗传和生化方法研究了模型系统秀丽隐杆线虫中胚芽颗粒的结构和功能。第一个目标是测试在已识别的胚芽颗粒成分中发现的核孔样蛋白结构域是否与核孔环境相互作用并扩展核孔环境。核孔蛋白通过该结构域相互作用，在细胞质和细胞核之间形成渗透性屏障。将测试含有这种核孔样结构域的胚芽颗粒蛋白，看看它们是否相互作用，以及是否与核孔相关成分相互作用。体内测试将研究活细胞中的这些相互作用。第二个目标测试了这样的假设：胚芽颗粒创造了一个微环境，可以选择性地排除进入核孔并调节胚系中的核输入。第三个目标是确定正确的胚芽颗粒组装所需的新组件。我已经对这些成分进行了全基因组 RNAi 筛选。通过该筛选鉴定出的基因类别开始揭示胚芽颗粒的功能机制。这些基因大多数都是保守的，因此可以告诉我们跨物种的胚芽颗粒功能。我们对线虫生殖细胞生物学的研究可能有助于了解生殖细胞、干细胞和癌细胞共有的调控机制。