Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208.
Mol Biol Cell. 2019 Jul 1;30(14):1691-1704. doi: 10.1091/mbc.E18-10-0666. Epub 2019 May 8.
Oocytes of many species lack centrioles and therefore form acentriolar spindles. Despite the necessity of oocyte meiosis for successful reproduction, how these spindles mediate accurate chromosome segregation is poorly understood. We have gained insight into this process through studies of the kinesin-4 family member Kif4 in mouse oocytes. We found that Kif4 localizes to chromosomes through metaphase and then largely redistributes to the spindle midzone during anaphase, transitioning from stretches along microtubules to distinct ring-like structures; these structures then appear to fuse together by telophase. Kif4's binding partner PRC1 and MgcRacGAP, a component of the centralspindlin complex, have a similar localization pattern, demonstrating dynamic spindle midzone organization in oocytes. Kif4 knockdown results in defective midzone formation and longer spindles, revealing new anaphase roles for Kif4 in mouse oocytes. Moreover, inhibition of Aurora B/C kinases results in Kif4 mislocalization and causes anaphase defects. Taken together, our work reveals essential roles for Kif4 during the meiotic divisions, furthering our understanding of mechanisms promoting accurate chromosome segregation in acentriolar oocytes.
许多物种的卵母细胞缺乏中心体,因此形成无中心体的纺锤体。尽管卵母细胞减数分裂对于成功繁殖是必要的,但这些纺锤体如何介导精确的染色体分离仍知之甚少。我们通过对小鼠卵母细胞中的驱动蛋白-4 家族成员 Kif4 的研究,深入了解了这一过程。我们发现 Kif4 通过中期定位到染色体上,然后在后期大部分重新分布到纺锤体的中部区域,从沿微管伸展转变为明显的环状结构;这些结构随后在末期似乎融合在一起。Kif4 的结合伙伴 PRC1 和中央纺锤体复合物的组成部分 MgcRacGAP 具有相似的定位模式,表明卵母细胞中纺锤体中部区域的动态组织。Kif4 的敲低导致中体形成缺陷和纺锤体变长,揭示了 Kif4 在小鼠卵母细胞中在后期的新作用。此外,抑制 Aurora B/C 激酶导致 Kif4 定位错误,并导致后期缺陷。总之,我们的工作揭示了 Kif4 在减数分裂过程中的重要作用,进一步加深了我们对无中心体卵母细胞中促进精确染色体分离的机制的理解。