Wellcome Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Scotland, UK.
Wellcome Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Scotland, UK
J Cell Biol. 2018 Oct 1;217(10):3431-3445. doi: 10.1083/jcb.201803172. Epub 2018 Aug 7.
The meiotic spindle in oocytes is assembled in the absence of centrosomes, the major microtubule nucleation sites in mitotic and male meiotic cells. A crucial, yet unresolved question in meiosis is how spindle microtubules are generated without centrosomes and only around chromosomes in the exceptionally large volume of oocytes. Here we report a novel oocyte-specific microtubule nucleation pathway that is essential for assembling most spindle microtubules complementarily with the Augmin pathway. This pathway is mediated by the kinesin-6 Subito/MKlp2, which recruits the γ-tubulin complex to the spindle equator to nucleate microtubules in oocytes. Away from chromosomes, Subito interaction with the γ-tubulin complex is suppressed by its N-terminal region to prevent ectopic microtubule assembly in oocytes. We further demonstrate in vitro that the Subito complex from ovaries can nucleate microtubules from pure tubulin dimers. Collectively, microtubule nucleation regulated by Subito drives spatially restricted spindle assembly in oocytes.
卵母细胞中的减数分裂纺锤体是在没有中心体的情况下组装的,中心体是有丝分裂和雄性减数分裂细胞中主要的微管核形成部位。在减数分裂中,一个关键但尚未解决的问题是,在卵子中异常大量的染色体周围,没有中心体的情况下,纺锤体微管是如何产生的。在这里,我们报告了一种新的卵母细胞特异性微管核形成途径,该途径对于组装大多数纺锤体微管与 Augmin 途径互补是必不可少的。该途径由驱动蛋白-6 Subito/MKlp2 介导,它将 γ-微管蛋白复合物招募到纺锤体赤道,在卵母细胞中核形成微管。在远离染色体的地方,Subito 与 γ-微管蛋白复合物的相互作用被其 N 端区域抑制,以防止卵母细胞中异位微管组装。我们进一步在体外证明,来自卵巢的 Subito 复合物可以从纯微管二聚体中核形成微管。总的来说,由 Subito 调节的微管核形成驱动卵母细胞中空间受限的纺锤体组装。