Clustering of centralspindlin is essential for its accumulation to the central spindle and the midbody.

Clustering of centralspindlin is essential for its accumulation to the central spindle and the midbody.
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DOI:
10.1016/j.cub.2009.10.050
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发表时间:
2009-12-15
期刊:
Current biology : CB
影响因子:
--
通讯作者:
Mishima M
Mishima M
中科院分区:
其他
文献类型:
--
作者:
Hutterer A;Glotzer M;Mishima M

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动物细胞的胞质分裂需要含有明显微管束的中央纺锤体和中间体。Centralspindlin是一种由驱动蛋白6和RhoGAP(Rho家族GTP酶激活蛋白)亚基组成的异源四聚体复合物,对于这些结构的形成至关重要。Centralspindlin变得精确定位于中央纺锤体,在那里它促进重要的细胞动力学调节因子的赤道募集。这些包括ECT2,小GTdR RhoA的激活剂,其控制卵裂沟的形成和侵入。Centralspindlin自身的RhoGAP结构域也有助于犁沟内移。最后,centralspindlin有助于招募染色体乘客复合体和控制终止的因子。尽管centralspindlin的本地化积累的重要性,该马达蛋白复合物突然集中到极间微管束的中心在后期的机制尚不清楚。在这里,我们表明,centralspindlin旅行沿着中央纺锤体微管作为高阶集群。centralspindlin的聚集对于体外微管成束和沿着微管的运动以及体内中间体的形成是至关重要的。这些数据支持centralspindlin聚类和微管组织的正反馈回路,这可能是其在胞质分裂期间独特定位的基础。
Cytokinesis in animal cells requires the central spindle and midbody which contain prominent microtubule bundles. Centralspindlin, a heterotetrameric complex consisting of Kinesin-6 and RhoGAP (Rho-family GTPase-activating protein) subunits, is essential for the formation of these structures. Centralspindlin becomes precisely localized to the central spindle where it promotes the equatorial recruitment of important cytokinetic regulators. These include ECT2, the activator of the small GTPase RhoA, which controls cleavage furrow formation and ingression. Centralspindlin’s own RhoGAP domain also contributes to furrow ingression. Finally, centralspindlin facilitates recruitment of the chromosome passenger complex and factors that control abscission. Despite the importance of localized accumulation of centralspindlin, the mechanism by which this motor protein complex suddenly concentrates to the centre of interpolar microtubule bundles during anaphase is unclear. Here, we show that centralspindlin travels along central spindle microtubules as higher-order clusters. Clustering of centralspindlin is critical for microtubule bundling and motility along microtubules in vitro, and for midbody formation in vivo. These data support a positive feedback loop of centralspindlin clustering and microtubule organization that may underlie its distinctive localization during cytokinesis.
CYK-4:中央纺锤体形成和细胞因子所需的RHO家族GTPase激活蛋白(GAP)。
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