Augmin: a protein complex required for centrosome-independent microtubule generation within the spindle.

Augmin: a protein complex required for centrosome-independent microtubule generation within the spindle.
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DOI:
10.1083/jcb.200711053
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发表时间:
2008-05-05
影响因子:
7.8
通讯作者:
Vale, Ronald D.
Vale, Ronald D.
中科院分区:
生物学1区
文献类型:
--
作者:
Goshima, Gohta;Mayer, Mirjam;Zhang, Nan;Stuurman, Nico;Vale, Ronald D.

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自从发现γ-微管蛋白以来,人们的注意力集中在它作为中心体微管成核剂的参与上。然而,γ-微管蛋白偏离中心体的错误定位并不抑制果蝇有丝分裂纺锤体的形成,这表明γ-微管蛋白的关键功能可能存在于其他地方。先前的RNA干扰(RNAi)筛选鉴定了将γ-微管蛋白定位于纺锤体微管所需的五个基因(Dgt 2 -6)。我们表明,Dgt蛋白相互作用,形成一个稳定的复合物。我们发现,纺锤体微管的产生大大减少后,敲低每个Dgt蛋白的RNAi。因此,我们命名为“augmin”的Dgt复合物具有增加微管数量的功能。Augmin RNAi后纺锤体微管生成减少,特别是在功能性中心体不存在的情况下,对有丝分裂纺锤体的形成和功能具有显著影响,导致动粒纤维形成减少,染色体错位和纺锤体双极性缺陷。我们还确定了Dgt 6的功能性人类同源物。我们的研究结果表明,一个重要的有丝分裂功能的γ-微管蛋白可能在于纺锤体,在那里Augmin和γ-微管蛋白的功能合作,以扩大微管的数量。
Since the discovery of γ-tubulin, attention has focused on its involvement as a microtubule nucleator at the centrosome. However, mislocalization of γ-tubulin away from the centrosome does not inhibit mitotic spindle formation in Drosophila melanogaster, suggesting that a critical function for γ-tubulin might reside elsewhere. A previous RNA interference (RNAi) screen identified five genes (Dgt2–6) required for localizing γ-tubulin to spindle microtubules. We show that the Dgt proteins interact, forming a stable complex. We find that spindle microtubule generation is substantially reduced after knockdown of each Dgt protein by RNAi. Thus, the Dgt complex that we name “augmin” functions to increase microtubule number. Reduced spindle microtubule generation after augmin RNAi, particularly in the absence of functional centrosomes, has dramatic consequences on mitotic spindle formation and function, leading to reduced kinetochore fiber formation, chromosome misalignment, and spindle bipolarity defects. We also identify a functional human homologue of Dgt6. Our results suggest that an important mitotic function for γ-tubulin may lie within the spindle, where augmin and γ-tubulin function cooperatively to amplify the number of microtubules.
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