Dynein light intermediate chains maintain spindle bipolarity by functioning in centriole cohesion.

Dynein light intermediate chains maintain spindle bipolarity by functioning in centriole cohesion.
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DOI:
10.1083/jcb.201408025
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发表时间:
2014-11-24
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Allan VJ
Allan VJ
中科院分区:
其他
文献类型:
--
作者:
Jones LA;Villemant C;Starborg T;Salter A;Goddard G;Ruane P;Woodman PG;Papalopulu N;Woolner S;Allan VJ

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在人类细胞和非洲爪哇胚胎中,细胞质动力蛋白轻中间链是维持中心粒凝聚力和形成双极纺锤体所必需的。胞浆动力蛋白1(Dynein)是一种负端导向的微管运动蛋白,具有多种细胞功能,包括在细胞分裂过程中。轻中间链(LIC;DYNC1LI1和2)在该复合体中的作用尚不清楚。在本论文中,我们使用小干扰RNA或吗啉寡核苷酸来耗尽人类细胞系和非洲爪哇早期胚胎中的LICs,以剖析LICs在细胞分裂中的作用。我们发现,尽管动力蛋白缺乏LICs驱动微管以正常速度滑动,但LICs是形成和维持双极纺锤体所必需的。在缺乏LICs的细胞中形成了具有包含单个中心粒的极的多极纺锤体,这表明它们是维持中心体完整性所必需的。抑制EG5可以挽救LIC耗竭后通过中心体分裂形成的多极纺锤体。这表明动力蛋白复合体在有丝分裂过程中维持中心粒凝聚力方面发挥了新的作用,这种作用被EG5所抵消。
Cytoplasmic dynein light intermediate chains are required for the maintenance of centriole cohesion and the formation of a bipolar spindle in both human cells and Xenopus embryos. Cytoplasmic dynein 1 (dynein) is a minus end–directed microtubule motor protein with many cellular functions, including during cell division. The role of the light intermediate chains (LICs; DYNC1LI1 and 2) within the complex is poorly understood. In this paper, we have used small interfering RNAs or morpholino oligonucleotides to deplete the LICs in human cell lines and Xenopus laevis early embryos to dissect the LICs’ role in cell division. We show that although dynein lacking LICs drives microtubule gliding at normal rates, the LICs are required for the formation and maintenance of a bipolar spindle. Multipolar spindles with poles that contain single centrioles were formed in cells lacking LICs, indicating that they are needed for maintaining centrosome integrity. The formation of multipolar spindles via centrosome splitting after LIC depletion could be rescued by inhibiting Eg5. This suggests a novel role for the dynein complex, counteracted by Eg5, in the maintenance of centriole cohesion during mitosis.
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