Rediscovery of the Nucleolinus

核仁的重新发现

• 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
• 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
• 来源: https://reporter.nih.gov/project-details/7902306
• 关键词: Ablation; Animals; Behavior; Biogenesis; Biological Models; Cancerous; Cell Nucleolus; Cell division; Cell physiology; Cell-Free System; Cells; Centrosome; Clams; Cytoplasm; Exposure to; Human; In Situ; Knowledge; Lasers; Lead; Link; Medicine; Meiosis; Microtubule-Organizing Center; Microtubules; Mitosis; Modeling; Neoplastic Cell Transformation; Oocytes; Organelles; Physiology; Play; Positioning Attribute; Preparation; Process; Research Personnel; Role; Science; Site; Testing; Tissues; prevent; public health relevance; research study

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）：核仁是存在于许多（如果不是全部）细胞中的细胞器。它在有丝分裂和肿瘤转化过程中的行为导致早期研究人员提出其在细胞分裂中的作用。然而，自发现以来 100 多年以来，人们对核仁的组成或功能几乎一无所知。由于它与核仁紧密相连，并且在大多数细胞中不易看见，因此经常被误认为是核仁的一部分。幸运的是，有一些细胞，例如北蛤（Spisula Solidissima）卵母细胞，其核仁是突出的。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。使用 Spisula 卵母细胞作为模型系统，我们进行了三个观察，这些观察可能将核仁与中心体（动物细胞的主要微管组织中心）联系起来。首先，中心体 RNA 在中心体形成之前特异性定位于核仁。其次，减数分裂过程中核仁的最后可见位置与减数分裂纺锤体极的位置一致，中心体在此处组织星体和纺锤体微管，为细胞分裂做准备。第三，在中心体形成之前核仁被消除的初步实验导致减数分裂受阻。这些观察结果使我们推测核仁是中心体从头形成所必需的。 Spisula 卵母细胞模型将用于通过两种互补的方法来检验这一假设：1）原位激光消融核仁，然后检查其对中心体组装和细胞分裂装置其他组件的影响； 2) 在无细胞系统中分析分离的核仁的中心体形成。我们预计这些实验将描绘出一个模型，其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中发挥作用。这一发现将代表我们对中心体生物发生的理解取得了根本性进展，并对细胞和生物医学科学具有广泛的影响。公共健康相关性：核仁是存在于许多组织细胞中的一种细胞器，50 多年来一直被认为参与细胞分裂和癌变。然而，我们缺乏对核仁组成和功能的了解，使我们无法了解它在这些过程中可能发挥的作用。因此，我们的研究结果可能会增加新的概念和实用信息，从而推动人类生理学或医学的广泛进步。