Identification of a novel Wnt5a-CK1ε-Dvl2-Plk1-mediated primary cilia disassembly pathway
Identification of a novel Wnt5a-CK1ε-Dvl2-Plk1-mediated primary cilia disassembly pathway
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DOI：
10.1038/emboj.2012.144
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发表时间：
2012-07-18
期刊：
影响因子：
11.4
通讯作者：
Lee, Kyung S.
中科院分区：
文献类型：
--
作者：
Lee, Kyung Ho;Johmura, Yoshikazu;Lee, Kyung S.
不活动的初级纤毛是一种触角样结构，其缺陷与广泛的病理学相关，包括发育障碍和癌症。虽然调节纤毛组装的机制已被广泛研究，纤毛拆卸如何调节仍然知之甚少。在这里，我们报告了Dishevelled 2（Dvl 2）和间期polo样激酶1（Plk 1）在初级纤毛解体中的意想不到的作用。我们证明，Dvl 2在S143和T224磷酸化的方式，需要两个非典型的Wnt 5a配体和酪蛋白激酶1 β（CK 1 β），这一事件是至关重要的，在细胞周期的早期阶段与Plk 1相互作用。所得到的Dvl 2-Plk 1复合物通过稳定HEF 1支架并激活其相关的Aurora-A（AurA）（一种初级纤毛解体至关重要的激酶）来介导Wnt 5a-CK 1 ε-Dvl 2依赖性初级纤毛解体。因此，通过Dvl 2-Plk 1复合物的形成，Plk 1通过将Wnt 5a诱导的生化步骤与HEF 1/AurA依赖性纤毛解体相联系，在初级纤毛解体中起着意想不到的作用。这项研究可能提供新的见解纤毛拆卸过程和各种纤毛相关疾病的机制。The EMBO Journal（2012）31，3104-3117. doi：10.1038/daj.2012.144; 2012年5月18日在线发布
Non-motile primary cilium is an antenna-like structure whose defect is associated with a wide range of pathologies, including developmental disorders and cancer. Although mechanisms regulating cilia assembly have been extensively studied, how cilia disassembly is regulated remains poorly understood. Here, we report unexpected roles of Dishevelled 2 (Dvl2) and interphase polo-like kinase 1 (Plk1) in primary cilia disassembly. We demonstrated that Dvl2 is phosphorylated at S143 and T224 in a manner that requires both non-canonical Wnt5a ligand and casein kinase 1 epsilon (CK1 epsilon), and that this event is critical to interact with Plk1 in early stages of the cell cycle. The resulting Dvl2-Plk1 complex mediated Wnt5a-CK1 epsilon-Dvl2-dependent primary cilia disassembly by stabilizing the HEF1 scaffold and activating its associated Aurora-A (AurA), a kinase crucially required for primary cilia disassembly. Thus, via the formation of the Dvl2-Plk1 complex, Plk1 plays an unanticipated role in primary cilia disassembly by linking Wnt5a-induced biochemical steps to HEF1/AurA-dependent cilia disassembly. This study may provide new insights into the mechanism underlying ciliary disassembly processes and various cilia-related disorders. The EMBO Journal (2012) 31, 3104-3117. doi: 10.1038/emboj.2012.144; Published online 18 May 2012