Ito Ami, Goshima Gohta
Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya 464-8602, Japan.
Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya 464-8602, Japan
J Cell Biol. 2015 Dec 7;211(5):999-1009. doi: 10.1083/jcb.201507001.
Depletion of Drosophila melanogaster Asp, an orthologue of microcephaly protein ASPM, causes spindle pole unfocusing during mitosis. However, it remains unclear how Asp contributes to pole focusing, a process that also requires the kinesin-14 motor Ncd. We show that Asp localizes to the minus ends of spindle microtubule (MT) bundles and focuses them to make the pole independent of Ncd. We identified a critical domain in Asp exhibiting MT cross-linking activity in vitro. Asp was also localized to, and focuses the minus ends of, intraspindle MTs that were nucleated in an augmin-dependent manner and translocated toward the poles by spindle MT flux. Ncd, in contrast, functioned as a global spindle coalescence factor not limited to MT ends. We propose a revised molecular model for spindle pole focusing in which Asp at the minus ends cross-links MTs at the pole and within the spindle. Additionally, this study provides new insight into the dynamics of intraspindle MTs by using Asp as a minus end marker.
果蝇微脑蛋白ASPM的同源物黑腹果蝇Asp的缺失会导致有丝分裂期间纺锤体极解聚。然而,目前尚不清楚Asp如何促进极聚焦,这一过程还需要驱动蛋白-14马达Ncd。我们发现Asp定位于纺锤体微管(MT)束的负端,并使其聚焦,从而使纺锤体极独立于Ncd。我们在体外鉴定出Asp中一个具有MT交联活性的关键结构域。Asp也定位于纺锤体内依赖augmin成核并通过纺锤体MT流移向两极的MT的负端,并使其聚焦。相比之下,Ncd作为一种全局纺锤体合并因子,并不局限于MT末端。我们提出了一种修订后的纺锤体极聚焦分子模型,其中负端的Asp在极处和纺锤体内交联MT。此外,本研究通过将Asp用作负端标记,为纺锤体内MT的动力学提供了新的见解。