Meiotic regulation of TPX2 protein levels governs cell cycle progression in mouse oocytes.

Meiotic regulation of TPX2 protein levels governs cell cycle progression in mouse oocytes.
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DOI:
10.1371/journal.pone.0003338
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发表时间:
2008-10-03
期刊:
影响因子:
3.7
通讯作者:
Verlhac MH
Verlhac MH
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Brunet S;Dumont J;Lee KW;Kinoshita K;Hikal P;Gruss OJ;Maro B;Verlhac MH

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在减数分裂过程中,雌配子的形成需要无中心纺锤体的装配。有丝分裂纺锤体由中心体组织,并通过染色体上的RanGTPase的局部激活。脊椎动物卵母细胞在减数分裂成熟的所有阶段都呈现以染色质为中心的RanGTP梯度。然而,这种梯度对于第一个减数分裂纺锤体的组装是必不可少的。为了了解这种减数分裂I的特性,我们研究了小鼠卵母细胞中的一个Ran靶点TPX2。引人注目的是,TPX2的活性通过其从减数分裂I到II的积累在蛋白质水平上受到控制。通过RNAi缺失和实时成像,我们发现TPX2通过两个不同的功能是纺锤体组装所必需的。它通过TACC3的磷酸化控制微管组装和纺锤杆完整性,TACC3是MTOCs活性的调节剂。我们发现体内减数分裂纺锤体的形成取决于至少一个Ran靶点TPX2的调控,而不是RanGTP梯度本身的调控。
Formation of female gametes requires acentriolar spindle assembly during meiosis. Mitotic spindles organize from centrosomes and via local activation of the RanGTPase on chromosomes. Vertebrate oocytes present a RanGTP gradient centred on chromatin at all stages of meiotic maturation. However, this gradient is dispensable for assembly of the first meiotic spindle. To understand this meiosis I peculiarity, we studied TPX2, a Ran target, in mouse oocytes. Strikingly, TPX2 activity is controlled at the protein level through its accumulation from meiosis I to II. By RNAi depletion and live imaging, we show that TPX2 is required for spindle assembly via two distinct functions. It controls microtubule assembly and spindle pole integrity via the phosphorylation of TACC3, a regulator of MTOCs activity. We show that meiotic spindle formation in vivo depends on the regulation of at least a target of Ran, TPX2, rather than on the regulation of the RanGTP gradient itself.
人类TPX2是将极光-A激酶靶向纺锤体所必需的。
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