初级纤毛中的ERICH3调节纤毛的形成以及纤毛运输和声波刺猬信号蛋白的定位。,Scientific Reports

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初级纤毛中的ERICH3调节纤毛的形成以及纤毛运输和声波刺猬信号蛋白的定位。
Scientific Reports ( IF 3.8 ) Pub Date : 2019-11-11 , DOI: 10.1038/s41598-019-52830-1
Mona Alsolami ₁ , Stefanie Kuhns ₁ , Manal Alsulami ₁ , Oliver E Blacque ₁

Affiliation

鞭毛内运输（IFT）对于基于微管的初级纤毛的形成和功能至关重要，纤毛在细胞表面起着感觉和信号传导的作用。由与分子马达相关联的IFT-A / B和BBS一些货物适配器组成，IFT将蛋白质转运到（顺行IFT）和从（逆行IFT）纤毛中转运出来。在这项研究中，我们确定了大多数未表征的ERICH3蛋白为哺乳动物初级纤毛的组成部分。ERICH3的丢失会导致异常纤毛变短，并导致IFT-A / B蛋白在睫状体尖端积聚，同时降低了睫状体逆行转运调节因子ARL13B，INPP5E和BBS5的水平。我们还显示，ERICH3睫状体定位需要ARL13B和BBSome组件。最后，ERICH3丢失导致声音刺猬信号（Shh）的正（平滑）和负（GPR161）调节剂以异常高的水平积聚在通路刺激细胞的纤毛中。在一起，这些发现确定ERICH3是初级纤毛的新成分，它调节纤毛长度和Shh信号分子的纤毛水平。我们提出，ERICH3在IFT逆行相关通路内起作用，以从纤毛中去除信号蛋白。

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ERICH3 in Primary Cilia Regulates Cilium Formation and the Localisations of Ciliary Transport and Sonic Hedgehog Signaling Proteins.

Intraflagellar transport (IFT) is essential for the formation and function of the microtubule-based primary cilium, which acts as a sensory and signalling device at the cell surface. Consisting of IFT-A/B and BBSome cargo adaptors that associate with molecular motors, IFT transports protein into (anterograde IFT) and out of (retrograde IFT) the cilium. In this study, we identify the mostly uncharacterised ERICH3 protein as a component of the mammalian primary cilium. Loss of ERICH3 causes abnormally short cilia and results in the accumulation of IFT-A/B proteins at the ciliary tip, together with reduced ciliary levels of retrograde transport regulators, ARL13B, INPP5E and BBS5. We also show that ERICH3 ciliary localisations require ARL13B and BBSome components. Finally, ERICH3 loss causes positive (Smoothened) and negative (GPR161) regulators of sonic hedgehog signaling (Shh) to accumulate at abnormally high levels in the cilia of pathway-stimulated cells. Together, these findings identify ERICH3 as a novel component of the primary cilium that regulates cilium length and the ciliary levels of Shh signaling molecules. We propose that ERICH3 functions within retrograde IFT-associated pathways to remove signaling proteins from cilia.

更新日期：2019-11-11

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