PDF(Pubmed)
Abstract：
The primary cilium is a microtubule-based sensory organelle that plays a critical role in signaling pathways and cell cycle progression. Defects in the structure and/or function of the primary cilium result in developmental diseases collectively known as ciliopathies. However, the constituents and regulatory mechanisms of the primary cilium are not fully understood. In recent years, the activity of the epigenetic modifier SMYD3 has been shown to play a key role in the regulation of cell cycle progression. However, whether SMYD3, a histone/lysine methyltransferase, contributes to the regulation of ciliogenesis remains unknown. Here, we report that SMYD3 drives ciliogenesis via the direct and indirect regulation of cilia-associated components. We show that SMYD3 is a novel component of the distal appendage and is required for centriolar appendage assembly. The loss of SMYD3 decreased the percentage of ciliated cells and resulted in the formation of stumpy cilia. We demonstrated that SMYD3 modulated the recruitment of centrosome proteins (Cep164, Fbf1, Ninein, Ttbk2 and Cp110) and the trafficking of intraflagellar transport proteins (Ift54 and Ift140) important for cilia formation and maintenance, respectively. In addition, we showed that SMYD3 regulated the transcription of cilia genes and bound to the promoter regions of C2cd3, Cep164, Ttbk2, Dync2h1 and Cp110. This study provides insights into the role of SMYD3 in cilia biology and suggests that SMYD3-mediated cilia formation/function may be relevant for cilia-dependent signaling in ciliopathies.
摘要：
初级纤毛是基于微管的感觉细胞器，在信号传导途径和细胞周期进程中起关键作用。原发性纤毛的结构和/或功能的缺陷导致统称为纤毛病的发育疾病。然而,初级纤毛的成分和调节机制尚不完全清楚。近年来,表观遗传修饰剂SMYD3的活性已被证明在细胞周期进程的调节中起关键作用。然而,SMYD3，一种组蛋白/赖氨酸甲基转移酶，有助于纤毛生成的调节仍然未知。这里,我们报道SMYD3通过直接和间接调节纤毛相关成分驱动纤毛发生。我们证明SMYD3是远端附件的新型组件，是中心附件组装所必需的。SMYD3的丢失降低了纤毛细胞的百分比，并导致了粗毛的形成。我们证明了SMYD3调节中心体蛋白(Cep164，Fbf1，Ninein，Ttbk2和Cp110）以及对纤毛形成和维持重要的步内转运蛋白（Ift54和Ift140）的运输，分别。此外,我们表明SMYD3调节纤毛基因的转录，并与C2cd3，Cep164，Ttbk2，Dync2h1和Cp110的启动子区域结合。这项研究提供了对SMYD3在纤毛生物学中的作用的见解，并表明SMYD3介导的纤毛形成/功能可能与纤毛依赖性信号有关。
