Toya Mika, Sato Masamitsu, Haselmann Uta, Asakawa Kazuhide, Brunner Damian, Antony Claude, Toda Takashi
Laboratory of Cell Regulation, Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
Nat Cell Biol. 2007 Jun;9(6):646-53. doi: 10.1038/ncb1593. Epub 2007 May 7.
The anchoring of microtubules to subcellular structures is critical for cell polarity and motility. Although the process of anchoring cytoplasmic microtubules to the centrosome has been studied in some detail, it is not known how spindle microtubules are anchored to the mitotic centrosome and, particularly, whether anchoring and nucleation of mitotic spindles are functionally separate. Here, we show that a fission yeast coiled-coil protein, Msd1, is required for anchoring the minus end of spindle microtubules to the centrosome equivalent, the spindle-pole body (SPB). msd1 deletion causes spindle microtubules to abnormally extend beyond SPBs, which results in chromosome missegregation. Importantly, this protruding spindle is phenocopied by the amino-terminal deletion mutant of Alp4, a component of the gamma-tubulin complex (gamma-TuC), which lacks the potential Msd1-interacting domain. We propose that Msd1 interacts with gamma-TuC, thereby specifically anchoring the minus end of microtubules to SPBs without affecting microtubule nucleation.
微管与亚细胞结构的锚定对于细胞极性和运动至关重要。尽管将细胞质微管锚定到中心体的过程已得到一定程度的详细研究，但尚不清楚纺锤体微管如何锚定到有丝分裂中心体，特别是有丝分裂纺锤体的锚定和成核在功能上是否相互独立。在此，我们表明裂殖酵母的一种卷曲螺旋蛋白Msd1是将纺锤体微管的负极锚定到相当于中心体的纺锤极体（SPB）所必需的。msd1缺失导致纺锤体微管异常延伸超出SPB，从而导致染色体错分离。重要的是，这种突出的纺锤体与γ-微管蛋白复合体（γ-TuC）的一个组分Alp4的氨基末端缺失突变体表现出相同的表型，该突变体缺乏潜在的与Msd1相互作用的结构域。我们提出Msd1与γ-TuC相互作用，从而将微管的负极特异性地锚定到SPB，而不影响微管成核。
