Department of Cell Biology, University of Oklahoma Health Sciences Center, 975 NE 10th Street, Oklahoma City, Oklahoma 73104, USA.
Nat Cell Biol. 2011 Apr;13(4):351-60. doi: 10.1038/ncb2183. Epub 2011 Mar 13.
The primary cilium is an antenna-like organelle that is dynamically regulated during the cell cycle. Ciliogenesis is initiated as cells enter quiescence, whereas resorption of the cilium precedes mitosis. The mechanisms coordinating ciliogenesis with the cell cycle are unknown. Here we identify the centrosomal protein Nde1 (nuclear distribution gene E homologue 1) 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 have 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 for understanding the transition from a quiescent to a proliferative state.
初级纤毛是一种类似天线的细胞器，在细胞周期中动态调节。纤毛发生始于细胞进入静止期，而纤毛的吸收则先于有丝分裂。协调纤毛发生与细胞周期的机制尚不清楚。在这里，我们将中心体蛋白 Nde1（核分布基因 E 同源物 1）鉴定为纤毛长度的负调控因子。Nde1 在有丝分裂中表达水平较高，在静止期表达水平较低，定位于起始初级纤毛的母中心粒。Nde1 缺失的细胞具有更长的纤毛，并且细胞周期重新进入的延迟与纤毛长度相关。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 Kupffer 泡的细胞数量减少以及左右图案缺陷。这些数据表明，Nde1 是一个协调纤毛长度与细胞周期进程的网络的组成部分，对于理解从静止到增殖状态的转变具有重要意义。
