Plk4 and Aurora A cooperate in the initiation of acentriolar spindle assembly in mammalian oocytes.
Plk4 and Aurora A cooperate in the initiation of acentriolar spindle assembly in mammalian oocytes.
复制标题
DOI：
10.1083/jcb.201606077
复制
发表时间：
2017-11-06
期刊：
影响因子：
--
通讯作者：
Glover DM
中科院分区：
文献类型：
--
作者：
Bury L;Coelho PA;Simeone A;Ferries S;Eyers CE;Eyers PA;Zernicka-Goetz M;Glover DM
哺乳动物卵母细胞在长时间停滞后在没有中心粒的情况下建立纺锤体，这对于减数分裂保真度至关重要。伯里等人。研究表明，这需要微管组织中心相关的 Aurora A 和 Plk4 的协同活动，它们通常存在于中心粒。在哺乳动物卵母细胞长期停滞后建立双极纺锤体对于减数分裂保真度和随后的发育至关重要。与体细胞相反，第一个减数分裂纺锤体在没有含有中心粒的中心体的情况下组装。 Ran-GTP 可以促进染色质附近的微管成核，但推测卵母细胞中多个心粒微管组织中心的活性还存在其他未知因素。我们现在证明 Aurora A 和 Plk4 激酶的部分重叠、非冗余功能有助于启动中心粒减数分裂 I 纺锤体的形成。单独使用耐药 Aurora A 可以显着挽救同时化学抑制两种激酶后微管成核的损失。耐药性 Plk4 可以增强 Aurora A 介导的救援，因此，Plk4 可以磷酸化并增强 Aurora A 的体外活性。这两种激酶的功能与 Ran 不同，后者会放大微管的生长。我们得出的结论是，当中心粒卵母细胞恢复减数分裂时，Aurora A 和 Plk4 是促进微管生长的限速因素。
Establishing the spindle in mammalian oocytes after their prolonged arrest occurs in the absence of centrioles and is crucial for meiotic fidelity. Bury et al. show that this requires concerted activity of microtubule organizing center–associated Aurora A and Plk4, which are usually found at centrioles. Establishing the bipolar spindle in mammalian oocytes after their prolonged arrest is crucial for meiotic fidelity and subsequent development. In contrast to somatic cells, the first meiotic spindle assembles in the absence of centriole-containing centrosomes. Ran-GTP can promote microtubule nucleation near chromatin, but additional unidentified factors are postulated for the activity of multiple acentriolar microtubule organizing centers in the oocyte. We now demonstrate that partially overlapping, nonredundant functions of Aurora A and Plk4 kinases contribute to initiate acentriolar meiosis I spindle formation. Loss of microtubule nucleation after simultaneous chemical inhibition of both kinases can be significantly rescued by drug-resistant Aurora A alone. Drug-resistant Plk4 can enhance Aurora A–mediated rescue, and, accordingly, Plk4 can phosphorylate and potentiate the activity of Aurora A in vitro. Both kinases function distinctly from Ran, which amplifies microtubule growth. We conclude that Aurora A and Plk4 are rate-limiting factors contributing to microtubule growth as the acentriolar oocyte resumes meiosis.
登录
查看更多内容
影响因子：
3.7
作者：
Brunet S;Dumont J;Lee KW;Kinoshita K;Hikal P;Gruss OJ;Maro B;Verlhac MH
通讯作者：
Verlhac MH
影响因子：
21.3
作者：
Habedanck, R;Stierhof, YD;Nigg, EA
通讯作者：
Nigg, EA
影响因子：
64.8
作者：
Heald, R;Tournebize, R;Karsenti, E
通讯作者：
Karsenti, E
影响因子：
2.7
作者：
Combelles, CMH;Albertini, DF
通讯作者：
Albertini, DF
影响因子：
9.2
作者：
Bettencourt-Dias, M;Rodrigues-Martins, A;Glover, DM
通讯作者：
Glover, DM