Mechanisms of mitotic spindle alignment by cytoplasmic microtubules and cell shape in Schizosaccharomyces pombe

有丝分裂纺锤体是由微管和运动蛋白组成的分子机器，在细胞分裂过程中将染色体分离成子细胞。在所有真核细胞中，相对于细胞分裂平面的纺锤体位置和排列对于染色体的成功分离是重要的。这个项目的主要目标是了解使主轴与细胞轴对齐的机制。我们使用分裂酵母Schizosaccharomyces pombe作为模型细胞，因为它只有多达10个微管，一个简单的圆柱形细胞形状，和高度发达的遗传学。我们最近表明，期间微管对早期分裂酵母纺锤体的排列是必需的，并且星体微管对后期纺锤体施加推力。该项目的具体目标是：1)通过间相微管解读早期纺锤体排列的分子机制；2)确定星状微管对纺锤体排列的贡献；3)揭示细胞形状在纺锤体排列中的作用。本项目发现的原理应适用于高等真核细胞微管组织和有丝分裂纺锤体定位的研究。

The mitotic spindle is a molecular machine made of microtubules and motor proteins, which segregates chromosomes into daughter cells during cell division. In all eukaryotic cells, spindle position and alignment with respect to the cell division plane is important for a successful segregation of the chromosomes. The main goal of this project is to understand the mechanisms that align the spindle with the cell axis. We use the fission yeast Schizosaccharomyces pombe as a model cell because it has only up to 10 microtubules, a simple cylindrical cell shape, and highly developed genetics. We have recently shown that interphase microtubules are required for the alignment of early fission yeast spindles, and that astral microtubules exert pushing forces on late spindles. The specific aims of the proposed project are: 1) to decipher the molecular mechanism of early spindle alignment by interphase microtubules, 2) to identify the contribution of astral microtubules to spindle alignment, and 3) to uncover the role of cell shape in spindle alignment. The principles discovered in this project should be applicable to studies of microtubule organization and mitotic spindle positioning in higher eukaryotic cells.