Trichoplein and Aurora A block aberrant primary cilia assembly in proliferating cells.
Trichoplein and Aurora A block aberrant primary cilia assembly in proliferating cells.
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DOI：
10.1083/jcb.201106101
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发表时间：
2012-04-30
期刊：
影响因子：
--
通讯作者：
Inagaki M
中科院分区：
文献类型：
--
作者：
Inoko A;Matsuyama M;Goto H;Ohmuro-Matsuyama Y;Hayashi Y;Enomoto M;Ibi M;Urano T;Yonemura S;Kiyono T;Izawa I;Inagaki M
毛纤毛- aura通路必须抑制初级纤毛组装才能使细胞退出G1。初级纤毛是一种类似天线的细胞器，它调节分化、感觉功能和信号转导。纤毛在G0/G1过渡期解体后，增殖细胞中纤毛的形成受到严格抑制。然而，这种抑制的机制尚不清楚。在本文中，我们发现在静止细胞中，三角蛋白从基底体中消失，而在增殖细胞中，它定位于母粒和子粒中心粒。外源表达trichoplein抑制血清饥饿细胞的原代纤毛组装，而核糖核酸干扰介导的耗竭诱导血清培养的原代纤毛组装。Trichoplein主要在G1期控制中心粒的Aurora A （AurA）激活。体外分析证实，trichoplein直接结合并激活AurA。利用毛锥蛋白突变体，我们证明毛锥蛋白对初级纤毛组装的抑制不仅需要其定位到中心粒的能力，还需要其结合和激活AurA的能力。Trichoplein或AurA敲低也会诱导G0/G1阻滞，但当同时敲低IFT-20阻止纤毛形成时，这种表型被逆转。这些数据表明，trichoplein-AurA通路通过持续抑制初级纤毛组装的关键作用，是G1进展所必需的。
The trichoplein–AurA pathway must suppress primary cilia assembly in order for cells to exit G1. The primary cilium is an antenna-like organelle that modulates differentiation, sensory functions, and signal transduction. After cilia are disassembled at the G0/G1 transition, formation of cilia is strictly inhibited in proliferating cells. However, the mechanisms of this inhibition are unknown. In this paper, we show that trichoplein disappeared from the basal body in quiescent cells, whereas it localized to mother and daughter centrioles in proliferating cells. Exogenous expression of trichoplein inhibited primary cilia assembly in serum-starved cells, whereas ribonucleic acid interference–mediated depletion induced primary cilia assembly upon cultivation with serum. Trichoplein controlled Aurora A (AurA) activation at the centrioles predominantly in G1 phase. In vitro analyses confirmed that trichoplein bound and activated AurA directly. Using trichoplein mutants, we demonstrate that the suppression of primary cilia assembly by trichoplein required its ability not only to localize to centrioles but also to bind and activate AurA. Trichoplein or AurA knockdown also induced G0/G1 arrest, but this phenotype was reversed when cilia formation was prevented by simultaneous knockdown of IFT-20. These data suggest that the trichoplein–AurA pathway is required for G1 progression through a key role in the continuous suppression of primary cilia assembly.
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