Ran induces spindle assembly by reversing the inhibitory effect of importin α on TPX2 activity

Ran induces spindle assembly by reversing the inhibitory effect of importin α on TPX2 activity
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DOI:
10.1016/s0092-8674(01)00193-3
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发表时间:
2001-01-12
期刊:
影响因子:
64.5
通讯作者:
Mattaj, IW
Mattaj, IW
中科院分区:
生物学1区
文献类型:
--
作者:
Gruss, OJ;Carazo-Salas, RE;Mattaj, IW

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与GTP结合的小GTP酶RAN是M期染色体诱导纺锤体形成所必需的。建议用高浓度的Ran.GTP包围M期染色质。我们发现,Ran.GTP在纺锤体形成中的作用需要TPX2,这是一种微管相关蛋白,以前已知的靶向微管的运动蛋白XKLP2。TPX2通常通过与核输入因子Importinα结合而失活,并通过Ran.GTP的作用取代Importinα。Ran.GTP和染色质诱导的M期微管组装需要TPX2,当超过游离Importinα时,TPX2参与介导微管自发组装。因此,核运输机械的部件起着调节M期纺锤体形成的作用。
The small GTPase Ran, bound to GTP, is required for the induction of spindle formation by chromosomes in M phase. High concentrations of Ran.GTP are proposed to surround M phase chromatin. We show that the action of Ran.GTP in spindle formation requires TPX2, a microtubule-associated protein previously known to target a motor protein, Xklp2, to microtubules. TPX2 is normally inactivated by binding to the nuclear import factor, importin alpha, and is displaced from importin alpha by the action of Ran.GTP. TPX2 is required for Ran.GTP and chromatin-induced microtubule assembly in M phase extracts and mediates spontaneous microtubule assembly when present in excess over free importin alpha. Thus, components of the nuclear transport machinery serve to regulate spindle formation in M phase.