Microtubule-sliding activity of a kinesin-8 promotes spindle assembly and spindle-length control.

Microtubule-sliding activity of a kinesin-8 promotes spindle assembly and spindle-length control.
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DOI:
10.1038/ncb2801
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发表时间:
2013-08
影响因子:
21.3
通讯作者:
--
中科院分区:
生物学1区
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分子马达在有丝分裂纺锤体的形成中起着关键作用,无论是通过控制单个微管的稳定性,还是通过交联和滑动微管阵列。驱动蛋白-8马达以其在控制微管动力学中的调节作用而闻名。它们含有微管不稳定活性,并在多种细胞类型和生物体中限制纺锤体长度。在这里,我们报告的第一次反平行微管滑动活动的芽殖酵母驱动蛋白-8,Kip 3。这种滑动活性的体内重要性是通过鉴定互补的Kip 3突变体来确定的,所述突变体分离滑动活性和微管去稳定活性。与驱动蛋白-5/Cin8结合,Kip 3的滑动活性促进双极纺锤体组装和维持基因组稳定性。我们提出了一个“滑动-拆卸”模型,其中Kip 3的滑动和不稳定的活动平衡在前后期。这有助于正常的主轴组装。然而,Kip 3的不稳定活性在后期占主导地位,抑制纺锤体伸长并最终促进纺锤体解体。
Molecular motors play critical roles in the formation of mitotic spindles, either through controlling the stability of individual microtubules, or by cross-linking 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 for the first time on an anti-parallel 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 kinesin-5/Cin8, the sliding activity of Kip3 promotes bipolar spindle assembly and the maintenance of genome stability. We propose a “slide-disassemble” model where Kip3’s sliding and destabilizing activity balance during pre-anaphase. This facilitates normal spindle assembly. However, Kip3’s destabilizing activity dominates in late anaphase, inhibiting spindle elongation and ultimately promoting spindle disassembly.
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