Institute of Molecular Biology, University of Oregon, Eugene, Oregon, United States of America.
PLoS Genet. 2023 Jan 6;19(1):e1010363. doi: 10.1371/journal.pgen.1010363. eCollection 2023 Jan.
The conserved two-component XMAP215/TACC modulator of microtubule stability is required in multiple animal phyla for acentrosomal spindle assembly during oocyte meiotic cell division. In C. elegans, XMAP215/zyg-9 and TACC/tac-1 mutant oocytes exhibit multiple and indistinguishable oocyte spindle assembly defects beginning early in meiosis I. To determine if these defects represent one or more early requirements with additional later and indirect consequences, or multiple temporally distinct and more direct requirements, we have used live cell imaging and fast-acting temperature-sensitive zyg-9 and tac-1 alleles to dissect their requirements at high temporal resolution. Temperature upshift and downshift experiments indicate that the ZYG-9/TAC-1 complex has multiple temporally distinct and separable requirements throughout oocyte meiotic cell division. First, we show that during prometaphase ZYG-9 and TAC-1 promote the coalescence of early pole foci into a bipolar structure, stabilizing pole foci as they grow and limiting their growth rate, with these requirements being independent of an earlier defect in microtubule organization that occurs upon nuclear envelope breakdown. Second, during metaphase, ZYG-9 and TAC-1 maintain spindle bipolarity by suppressing ectopic pole formation. Third, we show that ZYG-9 and TAC-1 also are required for spindle assembly during meiosis II, independently of their meiosis I requirements. The metaphase pole stability requirement appears to be important for maintaining chromosome congression, and we discuss how negative regulation of microtubule stability by ZYG-9/TAC-1 during oocyte meiotic cell division might account for the observed defects in spindle pole coalescence and stability.
保守的双组分 XMAP215/TACC 微管稳定性调节剂在多个动物门中对于卵母细胞减数分裂期间无中心体纺锤体的组装是必需的。在秀丽隐杆线虫中,XMAP215/zyg-9 和 TACC/tac-1 突变体卵母细胞在减数分裂 I 早期就表现出多种且无法区分的卵母细胞纺锤体组装缺陷。为了确定这些缺陷是否代表一个或多个早期的必需性,随后会产生更多的间接后果,或者是多个时间上不同且更直接的必需性,我们使用活细胞成像和快速作用的温度敏感型 zyg-9 和 tac-1 等位基因,以高时间分辨率剖析它们的需求。温度升温和降温实验表明,ZYG-9/TAC-1 复合物在卵母细胞减数分裂期间具有多个时间上不同且可分离的需求。首先,我们表明在前期,ZYG-9 和 TAC-1 促进早期极焦点聚合并形成双极结构,稳定极焦点的生长并限制其生长速度,这些需求独立于核膜破裂时发生的早期微管组织缺陷。其次,在中期,ZYG-9 和 TAC-1 通过抑制异位极的形成来维持纺锤体的双极性。第三,我们表明 ZYG-9 和 TAC-1 也独立于减数分裂 I 的需求,在减数分裂 II 期间也需要组装纺锤体。中期极稳定性的需求似乎对于保持染色体向心性很重要,我们讨论了 ZYG-9/TAC-1 在卵母细胞减数分裂期间如何通过负调控微管稳定性来解释观察到的纺锤体极聚合并稳定性缺陷。