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Functional analysis of cell-cycle dependent dynamics of components of the centrosome/spindle pole body

中心体/纺锤体极体成分的细胞周期依赖性动力学的功能分析

基本信息

批准号：
17570139
负责人：
TANAKA Kayoko
金额：
$ 2.24万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17570139/
关键词：
centrosome spindle pole body meiosis microtubule cell cycle

项目摘要

Upon commitment to sexual differentiation, fission yeast cells exchange the mating factor signal which induces dramatic remodeling of microtubule architecture to form an astral microtubule array emanating from the spindle pole body (SPB), the yeast centrosome equivalent organelle. During meiotic prophase, an oscillatory nuclear movement termed horsetail nuclear movement (HNM) takes place. HNM is led by the astral microtubule array aided by the dynein-dynactin complex and is proposed to facilitate the alignment of homologous chromosomes necessary for efficient meiotic recombination.I have identified a meiosis-specific SPB component Hrs1 (also known as Mcp6) and shown that Hrs1 is a key molecule to remodel microtubules into the horsetail-astral array (HAA). Deletion of Hrs1 impaired HAA formation, leading to compromised HNM. Ectopic expression of Hrs1 during the mitotic cell cycle resulted in the formation of a HAA-like astral microtubule array, which drove an oscillatory nuclear movement in interphase cells. Hrs1 interacted with components of the γ-tubulin complex (γ-TuC) as well as with a meiotic SPB component, suggesting that Hrs1 facilitates formation of the HAA, responsible for the vigorous HNM, by stabilizing connection between the SPB and minus ends of microtubules.Expression of Hrs1 is restricted to meiotic prophase. Upon the onset of meiosis I, Hrs1 abruptly disappeared from SPB even when it was forcibly expressed under the regulation of a strong nmt1 promoter. To see the effect of ectopic Hrs1 expression during meiosis, we isolated a few hrs1 mutants in which mutated Hrs1 proteins were stabilized at the SPB during meiosis I and II. in one of the mutants (hrs1.d10), relative timing of the spindle formation after the cessation of HNM was delayed and malformed spindle were observed. These results indicate a possible mechanism to down-regulate Hrs1 at the onset of meiosis I to ensure a smooth spindle formation.

在性分化的承诺，裂变酵母细胞交换交配因子的信号，诱导微管结构的显着重塑，形成一个星形微管阵列从纺锤体极体（SPB），酵母中心体等效的细胞器发出。在减数分裂前期，细胞核发生振荡运动，称为马尾核运动（HNM）。HNM是由动力蛋白-动力蛋白复合物辅助的星形微管阵列引导的，并被提议促进有效减数分裂重组所必需的同源染色体的对齐。我已经确定了减数分裂特异性SPB组分Hrs 1（也称为Mcp 6），并表明Hrs 1是将微管重塑成马尾星形阵列（HAA）的关键分子。Hrs 1的缺失损害了HAA的形成，导致HNM受损。Hrs 1在有丝分裂细胞周期中的异位表达导致了一个类似HAA的星形微管阵列的形成，它驱动了间期细胞中的振荡核运动。Hrs 1与γ-微管蛋白复合物（γ-TuC）和减数分裂的SPB组分相互作用，提示Hrs 1通过稳定SPB和微管负端之间的连接促进HAA的形成，HAA是HNM的主要原因，Hrs 1的表达仅限于减数分裂前期。在减数分裂I的发病，Hrs 1突然消失SPB，即使它被强制表达下的一个强大的nmt 1启动子的调节。为了观察Hrs 1在减数分裂过程中异位表达的影响，我们分离了几个hrs 1突变体，其中突变的Hrs 1蛋白在减数分裂I和II期间稳定在SPB。在其中一个突变体（hrs1.d10）中，HNM停止后纺锤体形成的相对时间延迟，并观察到畸形纺锤体。这些结果表明，一个可能的机制，下调Hrs 1在减数分裂I的发病，以确保顺利纺锤体形成。