Linking cytoplasmic dynein and transport of Rab8 vesicles to the midbody during cytokinesis by the doublecortin domain-containing 5 protein

Linking cytoplasmic dynein and transport of Rab8 vesicles to the midbody during cytokinesis by the doublecortin domain-containing 5 protein
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DOI:
10.1242/jcs.085407
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发表时间:
2011-12-01
影响因子:
4
通讯作者:
Reiner, Orly
Reiner, Orly
中科院分区:
生物学2区
文献类型:
--
作者:
Kaplan, Anna;Reiner, Orly

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有丝分裂的完成需要微管依赖性的膜向中间体的运输。在这里,我们确定了双皮质蛋白超家族的一个成员,含双皮质蛋白结构域的蛋白5(DCDC 5)在胞质分裂中的作用。DCDC 5是一种微管相关蛋白,在有丝分裂过程中以特异和动态的方式表达。我们发现,DCDC 5与细胞质动力蛋白和Rab 8(也称为Ras相关蛋白Rab-8A),以及Rab 8核苷酸交换因子Rabin 8(也称为Rab-3A相互作用蛋白)相互作用。在DCDC 5敲低后,中期到后期转换和胞质分裂的持续时间以及多核细胞的比例增加,而细胞活力降低。此外,敲低DCDC 5或添加动力蛋白抑制剂会损害高尔基体复合体衍生的Rab 8阳性囊泡进入中间体。这些发现表明,DCDC 5在介导Rab 8阳性囊泡的动力蛋白依赖性转运和协调晚期胞质分裂中起着重要作用。
Completion of mitosis requires microtubule-dependent transport of membranes to the midbody. Here, we identified a role in cytokinesis for doublecortin domain-containing protein 5 (DCDC5), a member of the doublecortin protein superfamily. DCDC5 is a microtubule-associated protein expressed in both specific and dynamic fashions during mitosis. We show that DCDC5 interacts with cytoplasmic dynein and Rab8 (also known as Ras-related protein Rab-8A), as well as with the Rab8 nucleotide exchange factor Rabin8 (also known as Rab-3A-interacting protein). Following DCDC5 knockdown, the durations of the metaphase to anaphase transition and cytokinesis, and the proportion of multinucleated cells increases, whereas cell viability decreases. Furthermore, knockdown of DCDC5 or addition of a dynein inhibitor impairs the entry of Golgi-complex-derived Rab8-positive vesicles to the midbody. These findings suggest that DCDC5 plays an important role in mediating dynein-dependent transport of Rab8-positive vesicles and in coordinating late cytokinesis.