Study of Hrs1 a meiosis specific component of microtubule organising centre in fission yeast S. pombe

裂殖酵母裂殖酵母微管组织中心减数分裂特异性成分Hrs1的研究

• 批准号: BB/F014597/1
• 负责人: Kayoko Tanaka
• 金额: $ 63.23万
• 依托单位: University of Leicester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FF014597%2F1
• 关键词: Study; Hrs1; meiosis; specific; component

Meiosis, the process by which gametes such as eggs and sperm are generated, is fundamental to living organisms that employ a sexual reproduction system for their propagation. The aim of sexual reproduction is to create genetic diversities, whereas the important genetic materials, which are required for essential biological activities, need to be faithfully inherited to the progenies. Meiosis is the process designed to accomplish this fiddly mission. All human cells contain two almost identical sets of genetic materials, one from the father and one from the mother. However gametes must contain only one set. This is crucial so that upon fusion of an egg and sperm, during the fertilization, the genetic content is returned to the two standard sets. Essentially, meiosis is a specialized form of cell division that halves the genetic content of parental cells. Furthermore, it allows a period of time during which one genetic set from the mother and one from the father can mix with each other leading to a unique and diverse set of genetic materials that give to the progenies their individuality. Separation of genetic materials during meiotic divisions occurs on a scaffold structure which is composed of microtubules (MTs). As their name implies, MTs are hollow rod-like tubes that are found within all cells. Specifically, they are fibrous polymers made up of the proteins alpha- and beta-tubulin, whose polymerisation and de-polymerisation enable MTs to grow and shrink. MTs contribute to the maintenance of the cell shape, the cell polarization, the cell movement and the intracellular transportation of other biological molecules and complexes. These important and diverse functions of MTs rely on their dynamic properties which, in turn, are regulated by MT-associated proteins. MTs emerge from a specialized structure within the cell called the MT organising centre (MTOC). MTOC contains another type of tubulin, gamma-tubulin, which, in association with several other proteins, forms a structure called gamma-tubulin complex (gamma-TuC) that acts as a nucleation seed for alpha/beta tubulin dimers to polymerise. In addition, many of the MT regulatory proteins are found to be concentrated at the MTOC. In this project, I aim to investigate MT regulation during meiotic cell division using yeast as a model organism. Many advances in understanding biology come from leads established in model systems. Fundamental cellular activities, such as ones performed by MTs, are conserved from yeasts to humans. A prime example of the impact of model systems upon the field is the identification of gamma-tubulin in a filamentous fungus A. nidulans. Search for homologous proteins of A. nidulans gamma-tubulin identified human gamma-tubulin. Another example is that extensive analyses employing budding yeast S. cerevisiae brought about identification and insights into conserved components of gamma-TuC. Following these leads I also aim to exploit in my work a highly tractable system the fission yeast S. pombe. In fission yeast, extensive conformational change of MT architecture takes place during meiosis. I have previously identified a protein called Hrs1, which appears on the MTOC during the early stage of meiosis, and induces a special MT conformation through this stage. I assume that there exists a regulatory system which makes Hrs1 to appear temporarily on the MTOC and assists the transition from one meiotic stage to the other. In this proposal, I will examine this assumption to obtain better insight into the MTOC regulation. Model systems are living test tubes which enable us to precisely examine working hypotheses in order to extract concepts applicable to other living organisms. Placing such information in the context of what we know about the MTOC of less tractable organisms provides valuable insights into the general MTOC function.

减数分裂是产生配子（如卵子和精子）的过程，是采用有性生殖系统进行繁殖的生物体的基础。有性生殖的目的是创造遗传多样性，而重要的遗传物质，这是必需的生物活动，需要忠实地遗传给后代。减数分裂就是为了完成这一繁琐的使命而设计的过程。所有的人类细胞都包含两组几乎相同的遗传物质，一组来自父亲，一组来自母亲。然而，配子必须只包含一套。这是至关重要的，以便在受精过程中卵子和精子融合时，遗传内容返回到两个标准集。从本质上讲，减数分裂是一种特殊的细胞分裂形式，它将亲本细胞的遗传内容减半。此外，它允许一段时间，在此期间，来自母亲的一个遗传组和来自父亲的一个遗传组可以相互混合，从而产生一组独特而多样的遗传物质，这些遗传物质赋予后代他们的个性。在减数分裂期间遗传物质的分离发生在由微管（MT）组成的支架结构上。顾名思义，MT是在所有细胞中发现的中空棒状管。具体来说，它们是由蛋白质α-和β-微管蛋白组成的纤维状聚合物，其聚合和解聚使MT能够生长和收缩。MT有助于维持细胞形状、细胞极化、细胞运动以及其他生物分子和复合物的胞内转运。MT的这些重要和多样的功能依赖于它们的动态特性，而这些动态特性又受到MT相关蛋白的调节。MT来自细胞内的一个专门结构，称为MT组织中心（MTOC）。MTOC含有另一种类型的微管蛋白，γ-微管蛋白，其与几种其他蛋白质结合形成称为γ-微管蛋白复合物（γ-TuC）的结构，其充当α/β微管蛋白二聚体聚合的成核种子。此外，许多MT调节蛋白被发现集中在MTOC。在这个项目中，我的目标是研究MT调节减数分裂细胞分裂使用酵母作为模式生物。许多理解生物学的进展来自于模型系统中建立的线索。从酵母到人类，基本的细胞活动（例如MT进行的活动）都是保守的。模型系统对该领域影响的一个主要例子是丝状真菌A. nidulans。寻找A. nidulans γ-微管蛋白鉴定人γ-微管蛋白。另一个例子是使用芽殖酵母S.酿酒酵母带来了对γ-TuC保守组分的鉴定和见解。根据这些线索，我也打算在我的工作中利用一个高度易处理的系统，裂变酵母S。粟酒在裂殖酵母中，MT结构在减数分裂期间发生广泛的构象变化。我以前已经确定了一个蛋白质称为Hrs 1，它出现在MTOC在减数分裂的早期阶段，并诱导一个特殊的MT构象通过这个阶段。我假设存在一个调节系统，使Hrs 1暂时出现在MTOC上，并协助从一个减数分裂阶段过渡到另一个减数分裂阶段。在本提案中，我将研究这一假设，以更好地了解MTOC法规。模型系统是活的试管，使我们能够精确地检查工作假设，以提取适用于其他生物体的概念。将这些信息置于我们对不太容易处理的生物体的MTOC的了解的背景下，可以为了解MTOC的一般功能提供有价值的见解。

项目成果

Transient structure associated with the spindle pole body directs meiotic microtubule reorganization in S. pombe.

• DOI: 10.1016/j.cub.2012.02.042
• 发表时间: 2012-04-10
• 期刊: CURRENT BIOLOGY
• 影响因子: 9.2
• 作者: Funaya, Charlotta;Samarasinghe, Shivanthi;Pruggnaller, Sabine;Ohta, Midori;Connolly, Yvonne;Mueller, Jan;Murakami, Hiroshi;Grallert, Agnes;Yamamoto, Masayuki;Smith, Duncan;Antony, Claude;Tanaka, Kayoko
• 通讯作者: Tanaka, Kayoko