Meiosis-specific stable binding of augmin to acentrosomal spindle poles promotes biased microtubule assembly in oocytes.
Meiosis-specific stable binding of augmin to acentrosomal spindle poles promotes biased microtubule assembly in oocytes.
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DOI：
10.1371/journal.pgen.1003562
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发表时间：
2013-06
期刊：
影响因子：
4.5
通讯作者：
Ohkura H
中科院分区：
文献类型：
--
作者：
Colombié N;Głuszek AA;Meireles AM;Ohkura H
在包括人类在内的许多动物的卵母细胞中，减数分裂纺锤体在没有中心体的情况下组装。目前尚不清楚多种途径如何促进纺锤体微管组装，以及它们在有丝分裂和减数分裂中是否受到不同的调节。 Augmin 是一种 γ-微管蛋白募集复合物，它通过在有丝分裂中沿现有微管生成新的微管来“放大”纺锤体微管。在这里，我们表明，在果蝇卵母细胞中，Augmin 对于染色质驱动的纺锤体微管组装是可有可无的，但对于两极附近的完整微管组装是必需的。纺锤体两极积累的 Augmin 水平与染色体会聚的程度密切相关。光漂白后的荧光恢复表明，Augmin 与卵母细胞中纺锤体的极性区域稳定结合，这与有丝分裂细胞中的情况不同，在有丝分裂细胞中，Augmin 与中期纺锤体短暂且均匀地结合。 γ-微管蛋白和驱动蛋白-14 Ncd 增强了这种稳定的关联。因此，我们建议 Augmin 的减数分裂特异性调节通过主动偏向纺锤体内微管生成位点来补偿卵母细胞中中心体的缺乏。尽管中心体是有丝分裂细胞中微管组装的主要位点，但在包括人类在内的许多动物的卵母细胞中，减数分裂纺锤体的组装不需要中心体。研究还表明，即使功能性中心体被人为消除，双极纺锤体也可以在有丝分裂细胞中组装。目前尚不清楚纺锤体微管如何在没有中心体的情况下组装，以及微管组装在有丝分裂和减数分裂中是否受到不同的调节。在这里，我们研究了果蝇卵母细胞中保守蛋白复合物 Augmin 的作用和调节，该复合物将 γ-微管蛋白招募到微管中以产生新的微管。我们发现，Augmin 的减数分裂特异性调节通过使微管组装偏向两极来替代卵母细胞中中心体活性的缺乏。由于 Augmin 在高等真核生物中广泛保守，我们的发现对于我们理解人类卵母细胞中染色体分离和错误分离具有重要意义。
In the oocytes of many animals including humans, the meiotic spindle assembles without centrosomes. It is still unclear how multiple pathways contribute to spindle microtubule assembly, and whether they are regulated differently in mitosis and meiosis. Augmin is a γ-tubulin recruiting complex which “amplifies” spindle microtubules by generating new microtubules along existing ones in mitosis. Here we show that in Drosophila melanogaster oocytes Augmin is dispensable for chromatin-driven assembly of bulk spindle microtubules, but is required for full microtubule assembly near the poles. The level of Augmin accumulated at spindle poles is well correlated with the degree of chromosome congression. Fluorescence recovery after photobleaching shows that Augmin stably associates with the polar regions of the spindle in oocytes, unlike in mitotic cells where it transiently and uniformly associates with the metaphase spindle. This stable association is enhanced by γ-tubulin and the kinesin-14 Ncd. Therefore, we suggest that meiosis-specific regulation of Augmin compensates for the lack of centrosomes in oocytes by actively biasing sites of microtubule generation within the spindle. Although centrosomes are the main sites of microtubule assembly in mitotic cells, the meiotic spindle assembles without centrosomes in the oocytes of many animals including humans. It has also been shown that bipolar spindles can be assembled in mitotic cells even when functional centrosomes are artificially eliminated. It is still unclear how spindle microtubules assemble without centrosomes, and whether microtubule assembly is regulated differently in mitosis and meiosis. Here we investigated the role and regulation of the conserved protein complex Augmin, which recruits γ-tubulin to microtubules to generate new microtubules, in Drosophila oocytes. We found that meiosis-specific regulation of Augmin substitutes for a lack of centrosomal activity in oocytes by biasing microtubule assembly towards poles. As Augmin is conserved widely in higher eukaryotes, our finding has an important implication in our understanding of chromosome segregation and mis-segregation in human oocytes.
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影响因子：
4.5
作者：
Hughes, Stacie E.;Gilliland, William D.;Hawley, R. Scott
通讯作者：
Hawley, R. Scott
影响因子：
64.8
作者：
Heald, R;Tournebize, R;Karsenti, E
通讯作者：
Karsenti, E
DOI：
10.1073/pnas.1106223108
发表时间：
2011-07-12
影响因子：
11.1
作者：
Johmura, Yoshikazu;Soung, Nak-Kyun;Lee, Kyung S.
通讯作者：
Lee, Kyung S.
影响因子：
4
作者：
Meunier, Sylvain;Vernos, Isabelle
通讯作者：
Vernos, Isabelle
影响因子：
21.3
作者：
Cullen, CF;Ohkura, H
通讯作者：
Ohkura, H