Rediscovery of the Nucleolinus

核仁的重新发现

基本信息

批准号：
7902306
负责人：
MARK Collin ALLIEGRO
金额：
$ 31.47万
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（由申请人提供）：核仁是许多（如果不是全部）中存在的细胞器。它在有丝分裂和肿瘤转化过程中的行为使早期研究者提出了在细胞分裂中的作用。然而，自发现发现以来已有100多年的历史了，几乎对核仁的组成或功能一无所知。因为它与核仁密切相关，并且在大多数细胞中不容易看到，所以通常被误认为是核仁的一部分。幸运的是，有一些细胞，例如冲浪蛤（Spisula solidissima）卵母细胞，其中核仁很突出。这种例外为核仁在细胞生理学和研究功能的机会中的作用提供了线索。我们使用Spisula卵母细胞作为模型系统，进行了三个观察结果，可能将核仁与中心体联系起来，这是动物细胞的主要微管组织中心。首先是中心体RNA在中心体形成之前特异性地定位于核仁。其次，减数分裂过程中核仁的最后一个可见位置与减数分裂纺锤极的部位相吻合，在那里，中心体组织了星体和纺锤微管以准备细胞分裂。第三，在核小体形成之前消融核仁的初步实验会导致减数分裂的阻塞。这些观察结果导致我们假设核仁是从头上心形成所必需的。 Spisula卵母细胞模型将在两种互补方法中用于检验该假设：1）原位核仁的激光消融，然后检查其对中心体和细胞分裂设备的其他成分的影响； 2）分析无细胞系统中分离的核酸盐的中心体形成。我们预计这些实验将描述一个模型，其中通过暴露于卵母细胞的细胞质来激活核仁，然后在形成第一个卵母细胞中心体（S）中起作用。这样的发现将代表我们对中心体生物发生的基本进步，并对细胞和生物医学科学具有广泛的影响。公共卫生相关性：核仁是许多组织细胞中存在的细胞器，被认为参与细胞分裂和癌性转化已有50多年了。然而，我们缺乏有关核仁组成和功能的知识，阻止了我们知道它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用信息，这可能会导致人类生理学或医学的广泛进步。