Nde1-mediated inhibition of ciliogenesis affects cell cycle re-entry.

Nde1-mediated inhibition of ciliogenesis affects cell cycle re-entry.
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DOI:
10.1038/ncb2183
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发表时间:
2011-04
影响因子:
21.3
通讯作者:
Tsiokas L
Tsiokas L
中科院分区:
生物学1区
文献类型:
--
作者:
Kim S;Zaghloul NA;Bubenshchikova E;Oh EC;Rankin S;Katsanis N;Obara T;Tsiokas L

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初级纤毛是一种天线状细胞器,在细胞周期中受到动态调节。纤毛发生在细胞进入静止状态时开始,而纤毛吸收在有丝分裂之前开始。纤毛发生与细胞周期的协调机制尚不清楚。在这里,我们发现中心体蛋白Nde1是纤毛长度的负调节因子。Nde1在有丝分裂时高水平表达,在静止时低水平表达,并定位于形成初级纤毛的母中心粒。缺乏Nde1的细胞表现出更长的纤毛和细胞周期重新进入的延迟,这与纤毛长度有关。在斑马鱼胚胎中敲低Nde1会导致纤毛长度增加,细胞分裂抑制,形成库普弗氏囊泡的细胞数量减少,以及左右图案缺陷。这些数据表明,Nde1是协调纤毛长度与细胞周期进程的网络的一个组成部分,并在细胞从静止状态向增殖状态的转变中起作用。
The primary cilium is an antenna-like organelle that is dynamically regulated during the cell cycle. Ciliogenesis is initiated as cells enter quiescence, while cilium resorption precedes mitosis. The mechanisms coordinating ciliogenesis with the cell cycle are unknown. Here we identify the centrosomal protein, Nde1, as a negative regulator of ciliary length. Nde1 is expressed at high levels in mitosis, low levels in quiescence and localizes at the mother centriole, which nucleates the primary cilium. Cells depleted of Nde1 show longer cilia and a delay in cell cycle re-entry that correlates with ciliary length. Knockdown of Nde1 in zebrafish embryos results in increased ciliary length, suppression of cell division, reduction of the number of cells forming the Kupffer’s vesicle, and left-right patterning defects. These data suggest that Nde1 is an integral component of a network coordinating ciliary length with cell cycle progression and have implications in the transition from quiescence to a proliferative state.
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