Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, 465 21st Avenue South, Nashville, TN 37232-8240, USA.
Curr Biol. 2010 Feb 23;20(4):374-80. doi: 10.1016/j.cub.2009.12.049. Epub 2010 Feb 11.
Motility is a fundamentally important property of most members of the kinesin superfamily, but a rare subset of kinesins are also able to alter microtubule dynamics. At kinetochore-microtubule plus ends, the kinesin-8 family member Kif18A is essential to align mitotic chromosomes at the spindle equator during cell division, but how it accomplishes this function is unclear. We report here that Kif18A is a plus-end-directed motor that inhibits the polymerization dynamics of microtubule plus ends without destabilizing them, distinguishing Kif18A from the budding yeast ortholog Kip3. In interphase cells, Kif18A uses this activity to reduce the overall dynamicity of microtubule plus ends and effectively constrains the distance over which plus ends grow and shrink. Our findings suggest that kinesin-8 family members have developed biochemically distinct activities throughout evolution and have implications for how Kif18A affects kinetochore-microtubule plus-end dynamics during mitosis in animal cells.
运动性是驱动蛋白超家族中大多数成员的基本重要性质,但驱动蛋白的一个罕见亚类也能够改变微管动力学。在动粒-微管正极末端,驱动蛋白-8 家族成员 Kif18A 在细胞分裂过程中对于在纺锤体赤道处排列有丝分裂染色体至关重要,但它如何完成此功能尚不清楚。我们在这里报告,Kif18A 是一个正极导向的运动蛋白,它抑制微管正极的聚合动力学,而不会使其不稳定,这将 Kif18A 与芽殖酵母同源物 Kip3 区分开来。在间期中,Kif18A 使用这种活性来降低微管正极的整体动力学,并有效地限制正极生长和收缩的距离。我们的研究结果表明,驱动蛋白-8 家族成员在整个进化过程中已经发展出了具有不同生化性质的活性,并且对于 Kif18A 如何影响动物细胞有丝分裂期间的动粒-微管正极动力学具有重要意义。