RAB35 depletion affects spindle formation and actin-based spindle migration in mouse oocyte meiosis.
RAB35 depletion affects spindle formation and actin-based spindle migration in mouse oocyte meiosis.
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DOI：
10.1093/molehr/gaz027
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发表时间：
2019-07
影响因子：
4
通讯作者：
Yu Zhang;Xiang Wan;Hong-Hui Wang;Meng-Hao Pan;Zhen-Nan Pan;Shao‐Chen Sun
中科院分区：
文献类型：
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作者：
Yu Zhang;Xiang Wan;Hong-Hui Wang;Meng-Hao Pan;Zhen-Nan Pan;Shao‐Chen Sun
哺乳动物卵母细胞的成熟涉及一个独特的不对称细胞分裂，其中减数分裂纺锤体的形成和肌动蛋白介导的纺锤体迁移到卵母细胞皮质是关键过程。在这里，我们报告的囊泡运输调节剂，RAB 35 GTdR，参与调节小鼠卵母细胞的细胞骨架动力学。在卵母细胞减数分裂过程中，RAB 35 GT3主要聚集在纺锤体周围和皮质。耗竭RAB 35的吗啉显微注射导致异常的极体挤出和不对称分裂缺陷，几乎一半的处理过的卵母细胞。我们还发现RAB 35影响SIRT 2和α达特的微管蛋白乙酰化，从而进一步调节微管稳定性和减数分裂纺锤体的形成。此外，我们发现RAB 35与卵母细胞中的RHOA相关，并调节肌动蛋白组装的ROCK-cofilin途径，这进一步促进了卵母细胞不对称分裂的纺锤体迁移。重要的是，将Myc-Rab 35 cRNA显微注射到去除RAB 35的卵母细胞中可以显著挽救这些缺陷。总之，我们的研究结果表明，在小鼠卵母细胞减数分裂的纺锤体稳定性和肌动蛋白介导的纺锤体迁移中，RAB 35 GTdR具有多重作用。
Mammalian oocyte maturation involves a unique asymmetric cell division, in which meiotic spindle formation and actin filament-mediated spindle migration to the oocyte cortex are key processes. Here, we report that the vesicle trafficking regulator, RAB35 GTPase, is involved in regulating cytoskeleton dynamics in mouse oocytes. RAB35 GTPase mainly accumulated at the meiotic spindle periphery and cortex during oocyte meiosis. Depletion of RAB35 by morpholino microinjection led to aberrant polar body extrusion and asymmetric division defects in almost half the treated oocytes. We also found that RAB35 affected SIRT2 and αTAT for tubulin acetylation, which further modulated microtubule stability and meiotic spindle formation. Additionally, we found that RAB35 associated with RHOA in oocytes and modulated the ROCK-cofilin pathway for actin assembly, which further facilitated spindle migration for oocyte asymmetric division. Importantly, microinjection of Myc-Rab35 cRNA into RAB35-depleted oocytes could significantly rescue these defects. In summary, our results suggest that RAB35 GTPase has multiple roles in spindle stability and actin-mediated spindle migration in mouse oocyte meiosis.