权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Rediscovery of the Nucleolinus

核仁的重新发现

基本信息

批准号：
8136556
负责人：
MARK Collin ALLIEGRO
金额：
$ 31.07万
依托单位：
MARINE BIOLOGICAL LABORATORY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-01 至 2013-08-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The nucleolinus is an organelle present in many, if not all cells. Its behavior during mitosis and neoplastic transformation led early investigators to propose a role in cell division. Yet, more than 100 years since its discovery, virtually nothing is known about the composition or function of the nucleolinus. Because it is closely apposed to the nucleolus and not easily visible in most cells, it is often mistaken as a part of the nucleolus. Fortunately, there are some cells, such as surf clam (Spisula solidissima) oocytes, in which the nucleolinus is prominent. Such exceptions provide clues to a role for the nucleolinus in cell physiology and opportunities to study function. Using Spisula oocytes as a model system, we have made three observations that potentially link the nucleolinus to the centrosome, the principle microtubule organizing center of animal cells. First is that centrosomal RNAs are specifically localized to the nucleolinus before centrosome formation. Second, the last visible position of the nucleolinus during meiosis coincides with the site of the meiotic spindle pole, where the centrosome organizes astral and spindle microtubules in preparation for cell division. Third, preliminary experiments in which the nucleolinus was ablated before centrosome formation resulted in a blockage of meiosis. These observations lead us to hypothesize that the nucleolinus is required for de novo centrosome formation. The Spisula oocyte model will be used to test this hypothesis in two complementary approaches: 1) laser ablation of the nucleolinus in situ followed by examination of its effects on assembly of centrosomes and other components of the cell division apparatus; 2) analysis of centrosome formation from isolated nucleolini in a cell-free system. We anticipate that these experiments will delineate a model in which the nucleolinus is activated by exposure to oocyte cytoplasm, and then functions in forming the first oocyte centrosome(s). Such a finding would represent a fundamental advance in our understanding of centrosome biogenesis and have broad implications for cell and biomedical sciences. PUBLIC HEALTH RELEVANCE: The nucleolinus is an organelle present in the cells of many tissues, and has been thought to participate in cell division and cancerous transformation for over 50 years. Yet, our lack of knowledge regarding nucleolinar composition and function prevent our knowing what roles it may play in these processes. It is therefore possible that the results of our study will add new conceptual and practical information that could lead to broad advances in human physiology or medicine.

描述(申请人提供)：核仁是存在于许多细胞中的细胞器，如果不是所有细胞的话。它在有丝分裂和肿瘤转化过程中的行为使早期研究人员提出了在细胞分裂中的作用。然而，在核仁被发现100多年后，人们对核仁的组成或功能几乎一无所知。因为它与核仁紧密相对，在大多数细胞中不易看到，所以经常被误认为是核仁的一部分。幸运的是，也有一些细胞，如青蛤卵母细胞，核仁是很突出的。这些例外为核仁在细胞生理学中的作用提供了线索，并为研究功能提供了机会。以Spisula卵母细胞为模型系统，我们观察到了三个可能将核仁与动物细胞的主要微管组织中心--中心体联系起来的现象。首先，中心体RNA在中心体形成之前特异性地定位于核仁。其次，核仁在减数分裂过程中的最后可见位置与减数分裂纺锤体极的位置一致，中心体在那里组织星形和纺锤体微管，为细胞分裂做准备。第三，在中心体形成之前去除核仁的初步实验导致减数分裂受阻。这些观察结果使我们假设核仁是形成新的中心体所必需的。Spisula卵母细胞模型将用两种互补的方法来检验这一假说：1)激光原位消融核仁，然后检查其对中心体和细胞分裂装置其他组件组装的影响；2)在无细胞系统中分析分离的核仁形成中心体。我们预计，这些实验将描绘出一种模型，在该模型中，核仁通过暴露于卵母细胞细胞质而被激活，然后在形成第一个卵母细胞中心体方面发挥作用(S)。这一发现将代表着我们对中心体生物发生的理解的根本性进步，并对细胞和生物医学科学具有广泛的影响。与公共卫生相关：核仁是存在于许多组织细胞中的细胞器，50多年来一直被认为参与细胞分裂和癌变。然而，我们缺乏关于核仁组成和功能的知识，这阻碍了我们了解核仁在这些过程中可能扮演的角色。因此，我们的研究结果可能会增加新的概念和实践信息，从而可能导致人类生理学或医学的广泛进步。