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Mixed-lineage leukemia protein 2 suppresses ciliary assembly by the modulation of actin dynamics and vesicle transport
Cell Discovery ( IF 13.0 ) Pub Date : 2019-06-25 , DOI: 10.1038/s41421-019-0100-3
Yang Yang , Huijie Hao , Xiaofan Wu , Song Guo , Yang Liu , Jie Ran , Te Li , Dengwen Li , Min Liu , Jun Zhou

Primary cilia are critically involved in the coordination of diverse signaling pathways and ciliary defects are associated with a variety of human diseases. The past decades have witnessed great progress in the core machinery orchestrating ciliary assembly. However, the upstream epigenetic cues that direct ciliogenesis remain elusive. Herein, we demonstrate that mixed-lineage leukemia protein 2 (MLL2), a histone methyltransferase, plays a negative role in ciliogenesis. RNA-sequencing analysis reveals that the expression of five actin-associated proteins is significantly downregulated in MLL2-depleted cells. Overexpression of these proteins partially rescues ciliary abnormality elicited by MLL2 depletion. Our data also show that actin dynamics is remarkably changed in MLL2-depleted cells, resulting in the impairment of cell adhesion, spreading, and motility. In addition, MLL2 depletion promotes ciliary vesicle trafficking to the basal body in an actin-related manner. Together, these results reveal that MLL2 inhibits ciliogenesis by modulating actin dynamics and vesicle transport, and suggest that alteration of MLL2 may contribute to the pathogenesis of cilium-associated diseases.



中文翻译:

混合谱系白血病蛋白2通过调节肌动蛋白动力学和囊泡转运来抑制睫状体组装

原发纤毛严重参与多种信号通路的协调,而纤毛缺陷与多种人类疾病有关。在过去的几十年中,核心机械协调睫毛组件取得了长足的进步。但是,直接纤毛发生的上游表观遗传线索仍然难以捉摸。在这里,我们证明,混合谱系白血病蛋白2(MLL2),组蛋白甲基转移酶,在纤毛发生中起负作用。RNA测序分析显示,在MLL2缺失的细胞中,五个肌动蛋白相关蛋白的表达明显下调。这些蛋白的过表达部分地挽救了MLL2耗竭引起的睫状体异常。我们的数据还表明,在MLL2耗尽的细胞中,肌动蛋白动力学发生了显着变化,从而导致细胞黏附,扩散,和动力。此外,MLL2耗竭以与肌动蛋白有关的方式促进睫状小泡向基体的运输。总之,这些结果表明,MLL2通过调节肌动蛋白动力学和囊泡运输来抑制纤毛发生,并表明MLL2的改变可能与纤毛相关疾病的发病机理有关。

更新日期:2019-11-18
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