The Christopher Chen Oocyte Biology Research Laboratory, Centre for Clinical Research, The University of Queensland, Herston, QLD, 4029, Australia.
Nat Commun. 2020 Jul 7;11(1):3393. doi: 10.1038/s41467-020-17088-6.
Meiotic divisions in oocytes are extremely asymmetric and require pre- and post-anaphase-onset phases of spindle migration. The latter induces membrane protrusion that is moulded around the spindle thereby reducing cytoplasmic loss. Here, we find that depleting the NAD biosynthetic enzyme, nicotinamide phosphoribosyl-transferase (Nampt), in mouse oocytes results in markedly longer spindles and compromises asymmetry. By analysing spindle speed in live oocytes, we identify a striking and transient acceleration after anaphase-onset that is severely blunted following Nampt-depletion. Slow-moving midzones of elongated spindles induce cortical furrowing deep within the oocyte before protrusions can form, altogether resulting in larger oocyte fragments being cleaved off. Additionally, we find that Nampt-depletion lowers NAD and ATP levels and that reducing NAD using small molecule Nampt inhibitors also compromises asymmetry. These data show that rapid midzone displacement is critical for extreme asymmetry by delaying furrowing to enable protrusions to form and link metabolic status to asymmetric division.
卵母细胞的减数分裂是极度不对称的，需要纺锤体迁移的前期和后期。后期诱导纺锤体周围的膜突起，从而减少细胞质的损失。在这里，我们发现，在小鼠卵母细胞中耗尽 NAD 生物合成酶烟酰胺磷酸核糖转移酶 (Nampt) 会导致纺锤体明显变长，并损害不对称性。通过分析活卵母细胞中的纺锤体速度，我们发现后期起始后会出现明显而短暂的加速，而 Nampt 耗竭后则会严重减弱。延长的纺锤体的缓慢移动的中部区域会在突起形成之前在卵母细胞内部诱导皮质皱襞，最终导致更大的卵母细胞碎片被切割下来。此外，我们发现 Nampt 耗竭会降低 NAD 和 ATP 水平，并且使用小分子 Nampt 抑制剂降低 NAD 也会损害不对称性。这些数据表明，快速的中部区域位移对于极度不对称性至关重要，因为它延迟了褶皱，从而使突起能够形成，并将代谢状态与不对称分裂联系起来。
