Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nat Cell Biol. 2013 Aug;15(8):948-57. doi: 10.1038/ncb2801. Epub 2013 Jul 14.
Molecular motors play critical roles in the formation of mitotic spindles, either through controlling the stability of individual microtubules, or by crosslinking and sliding microtubule arrays. Kinesin-8 motors are best known for their regulatory roles in controlling microtubule dynamics. They contain microtubule-destabilizing activities, and restrict spindle length in a wide variety of cell types and organisms. Here, we report an antiparallel microtubule-sliding activity of the budding yeast kinesin-8, Kip3. The in vivo importance of this sliding activity was established through the identification of complementary Kip3 mutants that separate the sliding activity and microtubule-destabilizing activity. In conjunction with Cin8, a kinesin-5 family member, the sliding activity of Kip3 promotes bipolar spindle assembly and the maintenance of genome stability. We propose a slide-disassemble model where the sliding and destabilizing activity of Kip3 balance during pre-anaphase. This facilitates normal spindle assembly. However, the destabilizing activity of Kip3 dominates in late anaphase, inhibiting spindle elongation and ultimately promoting spindle disassembly.
分子马达在有丝分裂纺锤体的形成中起着关键作用，它们可以通过控制单个微管的稳定性，或者通过交联和滑动微管阵列来实现。驱动蛋白-8 马达以其在控制微管动力学方面的调节作用而闻名。它们含有微管去稳定活性，并在多种细胞类型和生物体中限制纺锤体的长度。在这里，我们报告了酿酒酵母驱动蛋白-8（Kip3）的一个反平行微管滑动活性。通过鉴定分离滑动活性和微管去稳定活性的互补 Kip3 突变体，确定了这种滑动活性在体内的重要性。与 Cin8（一种驱动蛋白-5 家族成员）一起，Kip3 的滑动活性促进了双极纺锤体的组装和基因组稳定性的维持。我们提出了一个滑动-解组装模型，其中 Kip3 的滑动和去稳定活性在前期到中期平衡。这有助于正常的纺锤体组装。然而，Kip3 的去稳定活性在后期占据主导地位，抑制纺锤体的延伸，最终促进纺锤体的解体。
