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驱动蛋白-8 稳定动粒-微管相互作用。

kinesin-8 stabilizes the kinetochore-microtubule interaction.

机构信息

Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Japan.

Marine Biological Laboratory, Woods Hole, MA.

出版信息

J Cell Biol. 2019 Feb 4;218(2):474-488. doi: 10.1083/jcb.201807077. Epub 2018 Dec 11.

Abstract

Kinesin-8 is required for proper chromosome alignment in a variety of animal and yeast cell types. However, it is unclear how this motor protein family controls chromosome alignment, as multiple biochemical activities, including inconsistent ones between studies, have been identified. Here, we find that kinesin-8 (Klp67A) possesses both microtubule (MT) plus end-stabilizing and -destabilizing activity, in addition to kinesin-8's commonly observed MT plus end-directed motility and tubulin-binding activity in vitro. We further show that Klp67A is required for stable kinetochore-MT attachment during prometaphase in S2 cells. In the absence of Klp67A, abnormally long MTs interact in an "end-on" fashion with kinetochores at normal frequency. However, the interaction is unstable, and MTs frequently become detached. This phenotype is rescued by ectopic expression of the MT plus end-stabilizing factor CLASP, but not by artificial shortening of MTs. We show that human kinesin-8 (KIF18A) is also important to ensure proper MT attachment. Overall, these results suggest that the MT-stabilizing activity of kinesin-8 is critical for stable kinetochore-MT attachment.

摘要

驱动蛋白-8 对于多种动物和酵母细胞类型中染色体的正确排列是必需的。然而,目前尚不清楚该马达蛋白家族如何控制染色体的排列,因为已经确定了多种生化活性,包括研究之间不一致的活性。在这里,我们发现驱动蛋白-8(Klp67A)除了在体外具有通常观察到的驱动蛋白-8 的微管(MT)正极定向运动和微管结合活性之外,还具有 MT 正极稳定和去稳定活性。我们进一步表明,Klp67A 在 S2 细胞的早前期中对于稳定的动粒-MT 附着是必需的。在 Klp67A 缺失的情况下,异常长的 MT 以“端对端”的方式以正常频率与动粒相互作用。然而,这种相互作用是不稳定的,MT 经常会脱离。这种表型可以通过过表达 MT 正极稳定因子 CLASP 来挽救,但通过人为缩短 MT 则不能挽救。我们表明人源驱动蛋白-8(KIF18A)对于确保适当的 MT 附着也很重要。总的来说,这些结果表明驱动蛋白-8 的 MT 稳定活性对于稳定的动粒-MT 附着至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e484/6363442/0885ddee7a93/JCB_201807077_Fig1.jpg

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