Radford Sarah J, Go Allysa Marie M, McKim Kim S
Waksman Institute, Rutgers University, Piscataway, New Jersey 08854.
Department of Genetics, Rutgers University, Piscataway, New Jersey 08854.
Genetics. 2017 Feb;205(2):517-527. doi: 10.1534/genetics.116.194647. Epub 2016 Dec 7.
The oocyte spindle in most animal species is assembled in the absence of the microtubule-organizing centers called centrosomes. Without the organization provided by centrosomes, acentrosomal meiotic spindle organization may rely heavily on the bundling of microtubules by kinesin motor proteins. Indeed, the minus-end directed kinesin-14 NCD, and the plus-end directed kinesin-6 Subito are known to be required for oocyte spindle organization in Drosophila melanogaster How multiple microtubule-bundling kinesins interact to produce a functional acentrosomal spindle is not known. In addition, there have been few studies on the meiotic function of one of the most important microtubule-bundlers in mitotic cells, the kinesin-5 KLP61F. We have found that the kinesin-5 KLP61F is required for spindle and centromere symmetry in oocytes. The asymmetry observed in the absence of KLP61F depends on NCD, the kinesin-12 KLP54D, and the microcephaly protein ASP. In contrast, KLP61F and Subito work together in maintaining a bipolar spindle. We propose that the prominent central spindle, stabilized by Subito, provides the framework for the coordination of multiple microtubule-bundling activities. The activities of several proteins, including NCD, KLP54D, and ASP, generate asymmetries within the acentrosomal spindle, while KLP61F and Subito balance these forces, resulting in the capacity to accurately segregate chromosomes.
在大多数动物物种中,卵母细胞纺锤体是在没有称为中心体的微管组织中心的情况下组装而成的。由于缺乏中心体提供的组织作用,无中心体减数分裂纺锤体的组织可能严重依赖驱动蛋白运动蛋白对微管的捆绑作用。事实上,已知向负端移动的驱动蛋白-14 NCD和向正端移动的驱动蛋白-6 Subito是果蝇卵母细胞纺锤体组织所必需的。多种微管捆绑驱动蛋白如何相互作用以产生功能性的无中心体纺锤体尚不清楚。此外,对于有丝分裂细胞中最重要的微管捆绑蛋白之一驱动蛋白-5 KLP61F的减数分裂功能,相关研究很少。我们发现驱动蛋白-5 KLP61F是卵母细胞纺锤体和着丝粒对称性所必需的。在缺乏KLP61F时观察到的不对称性取决于NCD、驱动蛋白-12 KLP54D和小头蛋白ASP。相比之下,KLP61F和Subito共同作用以维持双极纺锤体。我们提出,由Subito稳定的突出的中央纺锤体为多种微管捆绑活动的协调提供了框架。包括NCD、KLP54D和ASP在内的几种蛋白质的活动在无中心体纺锤体内产生不对称性,而KLP61F和Subito平衡这些力量,从而使染色体能够准确分离。