Study of Meiotic Kinetochore Regulation

减数分裂着丝粒调控研究

• 批准号: 16K18487
• 负责人: 金 智慧
• 金额: $ 2.75万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2016
• 资助国家: 日本
• 起止时间: 2016-04-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16K18487/
• 关键词: meiosis; chromosome; kinetochore

Our previous study suggests that MEIKIN is required for maintenance of centromeric cohesion in anaphase I like moa1 in fission yeast. We have shown that centromeric localization of Shugoshin-2 (Sgo2), the protector of centromeric cohesin in mouse meiosis, is diminished and it may explain precocious sister chromatids separation during anaphase I in MEIKIN KO (knockout). To investigate the cause of SGO2 localization decrease in Meikin-/- spermatocytes, we examined Bub1 which are known to regulate SGO2 localization.Since kinetochore enrichment of Plk1 largely depends on MEIKIN in meiosis, these results raised the possibility that Plk1 activity might be required for Bub1 localization at kinetochore in mouse meiosis. In Plk1 inhibited wild-type spermatocytes by BI 2536 treatment, centromeric Bub1 signals are diminished in metaphase I which coincide with MEIKIN KO whereas no significant effects could be seen in diakinesis.Next we examined that Mps1 regulation for Bub1 localization in wild-type spermatocytes which are treated with the Mps1 inhibitor Reversine. Indeed, Mps1 specifically regulated Bub1 in diakinesis and showed milder effect in metaphase I than Plk1 inhibition. Finally, simultaneous inhibition of both Plk1 and Mps1 reduced additional levels of Bub1 not only in diakinesis but also metaphase I. We conclude that MEIKIN dependent Plk1 may recruit Bub1 to the kinetochore in meiosis I that regulates SGO2 localization on centromere. Furthermore, Plk1 and Mps1 redundantly regulate Bub1 in meiosis I.

我们以前的研究表明，MEIKIN是必需的维持着丝粒的凝聚力后期我一样moa 1在分裂酵母。我们已经表明，着丝粒定位的Shugoshin-2（Sgo 2），保护着丝粒粘连蛋白在小鼠减数分裂，是减少，它可以解释早熟的姐妹染色单体分离后期I MEIKIN KO（敲除）。为了研究SGO 2在Meikin-/-精母细胞中定位减少的原因，我们检测了已知调节SGO 2定位的Bub 1，由于Plk 1在减数分裂中的动粒富集在很大程度上依赖于MEIKIN，这些结果提出了Plk 1活性可能是Bub 1在小鼠减数分裂中定位于动粒所必需的。在BI 2536处理的Plk 1抑制的野生型精母细胞中，着丝粒Bub 1信号在中期I减弱，这与MEIKIN KO一致，而在终变期没有观察到显著影响。事实上，Mps 1特异性调节Bub 1终变期，并表现出温和的影响，在中期I比Plk 1抑制。最后，Plk 1和Mps 1的同时抑制不仅在终变期而且在中期I中降低了Bub 1的额外水平。我们得出结论，MEIKIN依赖Plk 1可能会招募Bub 1的着丝粒在减数分裂I，调节SGO 2的定位在着丝粒上。此外，Plk 1和Mps 1在减数分裂I中冗余地调节Bub 1。