The cohesion establishment factor Esco1 acetylates α-tubulin to ensure proper spindle assembly in oocyte meiosis.

The cohesion establishment factor Esco1 acetylates α-tubulin to ensure proper spindle assembly in oocyte meiosis.
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内聚建立因子 Esco1 乙酰化 α-微管蛋白,以确保卵母细胞减数分裂中纺锤体的正确组装。

DOI:
10.1093/nar/gky001
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发表时间:
2018-03-16
影响因子:
14.9
通讯作者:
Xiong B
Xiong B
中科院分区:
生物学2区
文献类型:
--
作者:
Lu Y;Li S;Cui Z;Dai X;Zhang M;Miao Y;Zhou C;Ou X;Xiong B

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据报道,Esco1作为一种内聚建立因子在有丝分裂细胞中介导染色体内聚和分离。然而,它在减数分裂中的确切作用尚未明确。本研究发现,在小鼠卵母细胞减数分裂成熟过程中,Esco1在细胞核和细胞质中均有表达和定位。通过siRNA显微注射去除Esco1导致减数分裂进程停滞,并伴有严重的纺锤体异常和染色体错位,这伴随着更高的着丝点-微管附着错误发生率和纺锤体组装检查点的激活。此外,Esco1的缺失导致微管稳定性受损,表现为对微管解聚药物诺可达唑的抗性减弱,乙酰化α-微管蛋白水平降低。相反,Esco1过表达导致α-微管蛋白超乙酰化和纺锤体缺陷。此外,我们发现Esco1与α-微管蛋白结合,并且是其乙酰化所必需的。在Esco1缺失的卵母细胞中,外源野生型Esco1的异位表达可以恢复α-微管蛋白乙酰化水平的降低,但不能恢复酶死亡的Esco1- g768d。纯化的野生型Esco1代替突变体Esco1- g768d体外乙酰化合成α-微管蛋白肽。总的来说,我们的数据表明,在卵母细胞减数分裂成熟过程中,Esco1作为微管调节剂具有一种新的功能,超出了其在染色体内聚中的传统作用。
Esco1 has been reported to function as a cohesion establishment factor that mediates chromosome cohesion and segregation in mitotic cells. However, its exact roles in meiosis have not been clearly defined. Here, we document that Esco1 is expressed and localized to both the nucleus and cytoplasm during mouse oocyte meiotic maturation. Depletion of Esco1 by siRNA microinjection causes the meiotic progression arrest with a severe spindle abnormality and chromosome misalignment, which is coupled with a higher incidence of the erroneous kinetochore–microtubule attachments and activation of spindle assembly checkpoint. In addition, depletion of Esco1 leads to the impaired microtubule stability shown by the weakened resistance ability to the microtubule depolymerizing drug nocodazole and the decreased level of acetylated α-tubulin. Conversely, overexpression of Esco1 causes hyperacetylation of α-tubulin and spindle defects. Moreover, we find that Esco1 binds to α-tubulin and is required for its acetylation. The reduced acetylation level of α-tubulin in Esco1-depleted oocytes can be restored by the ectopic expression of exogenous wild-type Esco1 but not enzymatically dead Esco1-G768D. Purified wild-type Esco1 instead of mutant Esco1-G768D acetylates the synthesized peptide of α-tubulin in vitro. Collectively, our data assign a novel function to Esco1 as a microtubule regulator during oocyte meiotic maturation beyond its conventional role in chromosome cohesion.
粘蛋白乙酰转移酶ECO1坐标RDNA复制和转录。
DOI: 10.1002/embr.201337974
发表时间: 2014-05
期刊: EMBO REPORTS
影响因子: 7.7
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