Poleward transport of TPX2 in the mammalian mitotic spindle requires dynein, Eg5, and microtubule flux.
Poleward transport of TPX2 in the mammalian mitotic spindle requires dynein, Eg5, and microtubule flux.
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DOI：
10.1091/mbc.e09-07-0601
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发表时间：
2010-03-15
影响因子：
3.3
通讯作者：
Wadsworth P
中科院分区：
文献类型：
--
作者：
Ma N;Tulu US;Ferenz NP;Fagerstrom C;Wilde A;Wadsworth P
TPX2是一种纺锤体组装因子，是MT在染色体附近组装所必需的。利用荧光的光激活，我们报道了TPX2在半纺锤体中被极向运输。TPX2的极向转运对Dynein或EG5的抑制以及MT通量的抑制很敏感。TPX2是一种RAN调节的纺锤体组装因子，对动粒纤维的形成和有丝分裂激酶Aurora A的激活是必需的。TPX2在纺锤体极点附近富含，在动点附近需要，这表明它在有丝分裂过程中经历了动态的重新定位。利用光激活技术，我们测量了PA-GFP-TPX2在有丝分裂纺锤体中的运动。TPX2在半主轴上向极移动，在区间和主轴两极附近保持静止。TPX2的极向转运对Dynein或EG5的抑制以及诺可达唑或Kif2a抗体抑制微管通量敏感。极地运输需要TPX2的C末端，这是一个与EG5相互作用的结构域。缺乏该结构域的TPX2的过表达导致动粒附近微管的过度形成，纺锤体组装的缺陷，并阻止有丝分裂的进行。我们的数据支持这样一个模型，即TPX2的极向运输下调了其动点附近的微管成核活性，并将动点产生的微管与动力蛋白联系起来，整合到纺锤体中。
TPX2 is a spindle assembly factor that is required for MT assembly near chromosomes. Using photoactivation of fluorescence, we report that TPX2 is transported poleward in the half-spindle. Poleward transport of TPX2 is sensitive to inhibition of dynein or Eg5, and to suppression of MT flux. TPX2 is a Ran-regulated spindle assembly factor that is required for kinetochore fiber formation and activation of the mitotic kinase Aurora A. TPX2 is enriched near spindle poles and is required near kinetochores, suggesting that it undergoes dynamic relocalization throughout mitosis. Using photoactivation, we measured the movement of PA-GFP-TPX2 in the mitotic spindle. TPX2 moves poleward in the half-spindle and is static in the interzone and near spindle poles. Poleward transport of TPX2 is sensitive to inhibition of dynein or Eg5 and to suppression of microtubule flux with nocodazole or antibodies to Kif2a. Poleward transport requires the C terminus of TPX2, a domain that interacts with Eg5. Overexpression of TPX2 lacking this domain induced excessive microtubule formation near kinetochores, defects in spindle assembly and blocked mitotic progression. Our data support a model in which poleward transport of TPX2 down-regulates its microtubule nucleating activity near kinetochores and links microtubules generated at kinetochores to dynein for incorporation into the spindle.
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影响因子：
7.8
作者：
Quintyne, N J;Gill, S R;Eckley, D M;Crego, C L;Compton, D A;Schroer, T A
通讯作者：
Schroer, T A
影响因子：
64.8
作者：
Heald, R;Tournebize, R;Karsenti, E
通讯作者：
Karsenti, E
DOI：
10.1083/jcb.109.2.637
发表时间：
1989-08
期刊：
The Journal of cell biology
影响因子：
--
作者：
Mitchison TJ
通讯作者：
Mitchison TJ
影响因子：
7.8
作者：
Cameron, LA;Yang, G;Salmon, ED
通讯作者：
Salmon, ED
影响因子：
3.3
作者：
Groen, Aaron C.;Maresca, Thomas J.;Mitchison, Timothy J.
通讯作者：
Mitchison, Timothy J.