Cyclin G-associated kinase promotes microtubule outgrowth from chromosomes during spindle assembly.
Cyclin G-associated kinase promotes microtubule outgrowth from chromosomes during spindle assembly.
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DOI：
10.1007/s00412-010-0267-8
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发表时间：
2010-08
期刊：
影响因子：
1.6
通讯作者：
Medema RH
中科院分区：
文献类型：
--
作者：
Tanenbaum ME;Vallenius T;Geers EF;Greene L;Mäkelä TP;Medema RH
在有丝分裂过程中，所有染色体必须附着在有丝分裂纺锤体的微管上，以确保正确的染色体分离。微管附着发生在染色体着丝粒区域的特殊结构处，称为动粒。这些着丝粒可以通过捕获中心体衍生的微管来生成微管附着物，但此外，它们本身也可以生成微管，随后微管与中心体衍生的微管整合形成有丝分裂纺锤体。在这里，我们进行了大规模 RNAi 筛选，并将细胞周期蛋白 G 相关激酶 (GAK) 鉴定为动粒/染色质微管生成的新型调节因子。 GAK 的这一功能需要其 C 端 J 结构域，这对于从内吞囊泡中回收网格蛋白至关重要。一致地，缺乏 GAK 的细胞显示有丝分裂纺锤体上网格蛋白水平大大降低，并且网格蛋白水平的降低也抑制着丝粒/染色体上微管的生成。最后，我们提出证据表明来自染色体的信号促进了网格蛋白与纺锤体的关联。这些结果确定了 GAK 和网格蛋白在动粒/染色体微管生长中的作用，并表明 GAK 通过网格蛋白控制染色体周围微管的生长。本文的在线版本 (doi:10.1007/s00412-010-0267-8) 包含补充材料，可供授权用户使用。
During mitosis, all chromosomes must attach to microtubules of the mitotic spindle to ensure correct chromosome segregation. Microtubule attachment occurs at specialized structures at the centromeric region of chromosomes, called kinetochores. These kinetochores can generate microtubule attachments through capture of centrosome-derived microtubules, but in addition, they can generate microtubules themselves, which are subsequently integrated with centrosome-derived microtubules to form the mitotic spindle. Here, we have performed a large scale RNAi screen and identify cyclin G-associated kinase (GAK) as a novel regulator of microtubule generation at kinetochores/chromatin. This function of GAK requires its C-terminal J-domain, which is essential for clathrin recycling from endocytic vesicles. Consistently, cells lacking GAK show strongly reduced levels of clathrin on the mitotic spindle, and reduction of clathrin levels also inhibits microtubule generation at kinetochores/chromosomes. Finally, we present evidence that association of clathrin with the spindle is promoted by a signal coming from the chromosomes. These results identify a role for GAK and clathrin in microtubule outgrowth from kinetochores/chromosomes and suggest that GAK acts through clathrin to control microtubule outgrowth around chromosomes. The online version of this article (doi:10.1007/s00412-010-0267-8) contains supplementary material, which is available to authorized users.
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DOI：
10.1083/jcb.200511132
发表时间：
2006-06-19
期刊：
The Journal of cell biology
影响因子：
--
作者：
Wong J;Fang G
通讯作者：
Fang G
影响因子：
7.5
作者：
Kelly AE;Funabiki H
通讯作者：
Funabiki H
影响因子：
9.2
作者：
Tulu, US;Fagerstrom, C;Wadsworth, P
通讯作者：
Wadsworth, P
影响因子：
4
作者：
Raaijmakers, Jonne A.;Tanenbaum, Marvin E.;Medema, Rene H.
通讯作者：
Medema, Rene H.
影响因子：
9.2
作者：
Tanenbaum, Marvin E.;Macurek, Libor;Medema, Rene H.
通讯作者：
Medema, Rene H.