Isoform-specific functions of Mud/NuMA mediate binucleation of Drosophila male accessory gland cells.

Isoform-specific functions of Mud/NuMA mediate binucleation of Drosophila male accessory gland cells.
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DOI:
10.1186/s12861-014-0046-5
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发表时间:
2014-12-20
影响因子:
--
通讯作者:
Adachi-Yamada T
Adachi-Yamada T
中科院分区:
生物学4区
文献类型:
--
作者:
Taniguchi K;Kokuryo A;Imano T;Minami R;Nakagoshi H;Adachi-Yamada T

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在标准的细胞分裂中,细胞先进行核分裂,然后进行胞质分裂。然而,一些细胞,如心肌细胞和肝细胞,可以通过有丝分裂而不进行胞质分裂来产生双核细胞。这种胞质分裂跳跃被认为是由于胞质分裂机制的抑制,如中心纺锤体或收缩环,但其调节机制尚不清楚。我们通过描述果蝇雄性附腺发育过程中的双核事件来研究它们,其中所有细胞都是双核的。附腺细胞在蚕蛹形成后50小时停止细胞周期,至蛹中期停止增殖5小时。然后,他们重新启动了细胞周期,并在55h同步进入M期。在这个时期,副腺细胞通过有丝分裂进行双核分裂,没有胞质分裂。双核细胞表现出标准的核分裂进程,但也表现出不寻常的特征,如非圆形,纺锤体沿心尖-基底轴取向,中央纺锤体组装不良。MUD是果蝇NUMA的同源物,它调控这三个特征的过程,经典的MudPBD和两个新鉴定的MudL和MUDS不同地调节它们:MudL抑制细胞圆形,MudPBD和MUDS沿心尖-基轴定向纺锤体,MUDS和MudL抑制中心纺锤体组装。重要的是,MUDS的过度表达甚至在标准的增殖细胞中也会诱导双核,例如在成像盘中的细胞。我们描述了果蝇雄性附腺中的双核现象,并研究了调节双核细胞异常形态的机制。我们证明了Mud,一种调节纺锤体方向的微管结合蛋白,参与了这一双核过程。我们认为,在双核过程中,Mud的三种结构不同的亚型所发挥的非典型功能调节细胞的圆形、纺锤体的取向和中心纺锤体的组装。我们还认为,在双核过程中,MUDS是触发胞质分裂跳跃的关键调节因子。本文的在线版本(doi:10.1186/s12861-0140046-5)包含补充材料,授权用户可以使用。
In standard cell division, the cells undergo karyokinesis and then cytokinesis. Some cells, however, such as cardiomyocytes and hepatocytes, can produce binucleate cells by going through mitosis without cytokinesis. This cytokinesis skipping is thought to be due to the inhibition of cytokinesis machinery such as the central spindle or the contractile ring, but the mechanisms regulating it are unclear. We investigated them by characterizing the binucleation event during development of the Drosophila male accessory gland, in which all cells are binucleate. The accessory gland cells arrested the cell cycle at 50 hours after puparium formation (APF) and in the middle of the pupal stage stopped proliferating for 5 hours. They then restarted the cell cycle and at 55 hours APF entered the M-phase synchronously. At this stage, accessory gland cells binucleated by mitosis without cytokinesis. Binucleating cells displayed the standard karyokinesis progression but also showed unusual features such as a non-round shape, spindle orientation along the apico-basal axis, and poor assembly of the central spindle. Mud, a Drosophila homolog of NuMA, regulated the processes responsible for these three features, the classical isoform MudPBD and the two newly characterized isoforms MudL and MudS regulated them differently: MudL repressed cell rounding, MudPBD and MudS oriented the spindle along the apico-basal axis, and MudS and MudL repressed central spindle assembly. Importantly, overexpression of MudS induced binucleation even in standard proliferating cells such as those in imaginal discs. We characterized the binucleation in the Drosophila male accessory gland and examined mechanisms that regulated unusual morphologies of binucleating cells. We demonstrated that Mud, a microtubule binding protein regulating spindle orientation, was involved in this binucleation. We suggest that atypical functions exerted by three structurally different isoforms of Mud regulate cell rounding, spindle orientation and central spindle assembly in binucleation. We also propose that MudS is a key regulator triggering cytokinesis skipping in binucleation processes. The online version of this article (doi:10.1186/s12861-014-0046-5) contains supplementary material, which is available to authorized users.
DOI: 10.1016/j.cell.2009.04.060
发表时间: 2009-07-23
期刊: CELL
影响因子: 64.5
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