Novel small GTPase subfamily capable of associating with tubulin is required for chromosome segregation
Novel small GTPase subfamily capable of associating with tubulin is required for chromosome segregation
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DOI：
10.1242/jcs.01347
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发表时间：
2004-09-15
影响因子：
4
通讯作者：
Katada, T
中科院分区：
文献类型：
--
作者：
Okai, T;Araki, Y;Katada, T
小的GTdR超家族，包括Ras、Rho/Rac、Rab、Arf和Ran亚家族，作为信号转导子调节细胞增殖和分化、肌动蛋白细胞骨架、膜运输和核转运。在这里，我们，确定新的GTP酶（人Gie 1和Gie 2），形成一个独特的小GTP酶的亚家族在其序列和细胞内功能。Gie代表“染色体平等分离所不可或缺的新型GTPase”，该亚家族在多细胞生物中是保守的。在哺乳动物细胞中表达显性负性Gie突变体或在果蝇S2细胞中使用RNA干扰敲低Gie转录物诱导染色体分离的异常形态。Gie蛋白具有与微管蛋白结合的能力，并在有丝分裂后期与微管一起定位于纺锤体中间区。此外，Gie突变体，缺乏推定的效应域，但有微管蛋白结合能力诱导微核形成的过度表达。因此，这是第一个报告表明，一个小的GTdR亚家族能够与微管可能参与染色体分离。
The small GTPase superfamily, which includes the Ras, Rho/Rac, Rab, Arf and Ran subfamilies, serves as a signal transducer to regulate cell proliferation and differentiation, actin cytoskeleton, membrane trafficking, and nuclear transport. Here, we,identify novel GTPases (human Gie1 and Gie2) that form a distinct subfamily of the small GTPases in terms of their sequences and intracellular function. Gie stands for 'novel GTPase indispensable for equal segregation of chromosomes', and this subfamily is conserved in multicellular organisms. Expression of dominant-negative Gie mutants in mammalian cells or knockdown of Gie transcripts using RNA interference in Drosophila S2 cells induced abnormal morphology in the chromosome segregation. Gie protein has ability to bind to tubulin and localizes with microtubules on the spindle mid-zone in late mitosis. Furthermore, overexpression of Gie mutants that lack putative effector domains but have tubulin-binding ability induced micronucleus formation. Thus, this is the first report showing that a small GTPase subfamily capable of associating with microtubules might be involved in chromosome segregation.