Park Seon-Ah, Yoo Hyunjeong, Seol Jae Hong, Rhee Kunsoo
Department of Biological Sciences, Seoul National University, Seoul 08826, Korea.
Department of Biological Sciences, Seoul National University, Seoul 08826, Korea
Biol Open. 2019 Aug 9;8(8):bio043828. doi: 10.1242/bio.043828.
Cilia are extended from mother centrioles in quiescent G0/G1 cells and retracted in dividing cells. Diverse post-translational modifications play roles in the assembly and disassembly of the cilium. Here, we examined class I histone deacetylases (HDACs) as positive regulators of cilia assembly in serum-deprived RPE1 and HK2 cells. We observed that the number of cells with cilia was significantly reduced in HDAC3- and HDAC8-depleted cells. The ciliary length also decreased in HDAC3- and HDAC8-depleted cells compared to that in control cells. A knockdown-rescue experiment showed that wild-type HDAC3 and HDAC8 rescued the cilia assembly and ciliary length in HDAC3- and HDAC8-depleted cells, respectively; however, deacetylase-dead HDAC3 and HDAC8 mutants did not. This suggests that deacetylase activity is critical for both HDAC3 and HDAC8 function in cilia assembly and ciliary length control. This is the first study to report that HDACs are required for the assembly and elongation of the primary cilia.
纤毛在静止的G0/G1期细胞中从母中心粒延伸出来，并在分裂细胞中缩回。多种翻译后修饰在纤毛的组装和拆卸中发挥作用。在这里，我们研究了I类组蛋白去乙酰化酶（HDACs）作为血清饥饿的RPE1和HK2细胞中纤毛组装的正调控因子。我们观察到，在HDAC3和HDAC8缺失的细胞中，有纤毛的细胞数量显著减少。与对照细胞相比，HDAC3和HDAC8缺失的细胞中的纤毛长度也缩短了。敲低挽救实验表明，野生型HDAC3和HDAC8分别挽救了HDAC3和HDAC8缺失细胞中的纤毛组装和纤毛长度；然而，去乙酰化酶失活的HDAC3和HDAC8突变体则不能。这表明去乙酰化酶活性对于HDAC3和HDAC8在纤毛组装和纤毛长度控制中的功能至关重要。这是第一项报道HDACs是初级纤毛组装和延长所必需的研究。
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