Graduate School of Medical Science and Engineering, KAIST, Daejeon 305-701, Korea.
1] Department of Biological Sciences, KAIST, Daejeon 305-701, Korea [2] Center for Cognition and Sociality, Institute for Basic Science (IBS), Daejeon 305-701, Korea.
Nat Commun. 2015 Apr 7;6:6781. doi: 10.1038/ncomms7781.
Primary cilia exert a profound impact on cell signalling and cell cycle progression. Recently, actin cytoskeleton destabilization has been recognized as a dominant inducer of ciliogenesis, but the exact mechanisms regulating ciliogenesis remain poorly understood. Here we show that the actin cytoskeleton remodelling controls ciliogenesis by regulating transcriptional coactivator YAP/TAZ as well as ciliary vesicle trafficking. Cytoplasmic retention of YAP/TAZ correlates with active ciliogenesis either in spatially confined cells or in cells treated with an actin filament destabilizer. Moreover, knockdown of YAP/TAZ is sufficient to induce ciliogenesis, whereas YAP/TAZ hyperactivation suppresses serum starvation-mediated ciliogenesis. We also identify actin remodelling factors LIMK2 and TESK1 as key players in the ciliogenesis control network in which YAP/TAZ and directional vesicle trafficking are integral components. Our work provides new insights for understanding the link between actin dynamics and ciliogenesis.
初级纤毛对细胞信号转导和细胞周期进程有深远的影响。最近，肌动蛋白细胞骨架的不稳定被认为是纤毛发生的主要诱导剂，但调节纤毛发生的确切机制仍知之甚少。在这里，我们表明，肌动蛋白细胞骨架重塑通过调节转录共激活因子 YAP/TAZ 以及纤毛囊泡运输来控制纤毛发生。YAP/TAZ 的细胞质保留与空间受限细胞或用肌动蛋白丝不稳定处理的细胞中的活跃纤毛发生相关。此外，YAP/TAZ 的敲低足以诱导纤毛发生，而 YAP/TAZ 的过度激活抑制血清饥饿介导的纤毛发生。我们还确定肌动蛋白重塑因子 LIMK2 和 TESK1 是纤毛发生控制网络中的关键参与者，其中 YAP/TAZ 和定向囊泡运输是整体组成部分。我们的工作为理解肌动蛋白动力学和纤毛发生之间的联系提供了新的见解。
