Changing roles of aurora-B kinase in two life cycle stages of Trypanosoma brucei

Changing roles of aurora-B kinase in two life cycle stages of Trypanosoma brucei
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DOI:
10.1128/ec.00129-06
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发表时间:
2006-07-01
期刊:
影响因子:
--
通讯作者:
Wang, C. C.
Wang, C. C.
中科院分区:
其他
文献类型:
--
作者:
Li, Ziyin;Wang, C. C.

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极光- b激酶是染色体分离和细胞分裂所必需的染色体客运蛋白。在原环型的布氏锥虫中,极光- b激酶同源物ThAUK1的缺失抑制纺锤体形成、有丝分裂、细胞分裂和细胞器复制,而不改变细胞形态。在本研究中,TbAUK1的RNA干扰敲低或失活突变体TbAUK1K58R在血流形态中的过表达也会导致纺锤体形成、染色体分离和细胞质分裂的缺陷,但可以进行多轮核DNA合成、核核增殖以及着丝体、基体和鞭毛的持续复制。典型的锥虫形态消失为充满微管的增大的圆形。由此可见,TbAUK1在调节锥虫两个发育阶段的细胞分裂中具有不同的作用机制。虽然它对前环形式的有丝分裂、细胞器复制和细胞质分裂施加严格控制,但在血流形式中,它调节细胞质分裂而不严格控制核DNA合成或细胞器复制。这些差异背后的分子基础仍有待探索。
Aurora-B kinase is a chromosomal passenger protein essential for chromosome segregation and cytokinesis. In the procyclic form of Trypanosoma brucei, depletion of an aurora-B kinase homologue ThAUK1 inhibited spindle formation, mitosis, cytokinesis, and organelle replication without altering cell morphology. In the present study, an RNA interference knockdown of TbAUK1 or overexpression of inactive mutant TbAUK1K58R in the bloodstream form also resulted in defects in spindle formation, chromosome segregation, and cytokinesis but allowed multiple rounds of nuclear DNA synthesis, nucleolus multiplication, and continuous replication of kinetoplast, basal body, and flagellum. The typical trypanosome morphology was lost to an enlarged round shape filled with microtubules. It is thus apparent that there are distinctive mechanisms of action of TbAUK1 in regulating cell division between the two developmental stages of trypanosome. While it exerts a tight control on mitosis, organelle replication, and cytokinesis in the procyclic form, it regulates cytokinesis without rigid control over either nuclear DNA synthesis or organelle replication in the bloodstream form. The molecular basis underlining these discrepancies remains to be explored.