Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Department of Molecular Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
Genetics. 2021 Jun 24;218(2). doi: 10.1093/genetics/iyab050.
The mitotic spindle is resilient to perturbation due to the concerted, and sometimes redundant, action of motors and microtubule-associated proteins. Here, we utilize an inducible ectopic microtubule nucleation site in the nucleus of Saccharomyces cerevisiae to study three necessary steps in the formation of a bipolar array: the recruitment of the γ-tubulin complex, nucleation and elongation of microtubules (MTs), and the organization of MTs relative to each other. This novel tool, an Spc110 chimera, reveals previously unreported roles of the microtubule-associated proteins Stu2, Bim1, and Bik1, and the motors Vik1 and Kip3. We report that Stu2 and Bim1 are required for nucleation and that Bik1 and Kip3 promote nucleation at the ectopic site. Stu2, Bim1, and Kip3 join their homologs XMAP215, EB1 and kinesin-8 as promoters of microtubule nucleation, while Bik1 promotes MT nucleation indirectly via its role in SPB positioning. Furthermore, we find that the nucleation activity of Stu2 in vivo correlates with its polymerase activity in vitro. Finally, we provide the first evidence that Vik1, a subunit of Kar3/Vik1 kinesin-14, promotes microtubule minus end focusing at the ectopic site.
有丝分裂纺锤体具有抗扰性,这是由于马达和微管相关蛋白的协同作用,有时甚至是冗余作用。在这里,我们利用酿酒酵母核内可诱导的异位微管成核位点来研究形成双极阵列的三个必要步骤:γ-微管蛋白复合物的募集、微管(MTs)的成核和延伸,以及 MTs 之间的相对组织。这种新型工具,即 Spc110 嵌合体,揭示了微管相关蛋白 Stu2、Bim1 和 Bik1 以及马达 Vik1 和 Kip3 的以前未报道的作用。我们报告说,Stu2 和 Bim1 是成核所必需的,而 Bik1 和 Kip3 促进异位位点的成核。Stu2、Bim1 和 Kip3 与它们的同源物 XMAP215、EB1 和驱动蛋白-8 一起成为微管成核的促进剂,而 Bik1 通过其在 SPB 定位中的作用间接促进 MT 成核。此外,我们发现 Stu2 在体内的成核活性与其在体外的聚合酶活性相关。最后,我们提供了第一个证据表明,Kar3/Vik1 动力蛋白-14 的亚基 Vik1 促进了异位位点微管末端聚焦。