DGKδ triggers endoplasmic reticulum release of IFT88-containing vesicles destined for the assembly of primary cilia.

DGKδ triggers endoplasmic reticulum release of IFT88-containing vesicles destined for the assembly of primary cilia.
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DGK delta 触发内质网释放含有 IFT88 的囊泡,这些囊泡用于初级纤毛的组装

DOI:
10.1038/s41598-017-05680-8
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发表时间:
2017-07-13
期刊:
影响因子:
4.6
通讯作者:
Cheng SY
Cheng SY
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ding J;Shao L;Yao Y;Tong X;Liu H;Yue S;Xie L;Cheng SY

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形态发生因子Sonic hedgehog(Shh)通过初级纤毛发出信号,初级纤毛依赖于鞭毛内运输来维持其结构完整性和功能。然而,蛋白质和脂质货物从它们的合成位点递送到初级纤毛的过程仍然没有得到很好的表征。在这里,我们报告,二酰基甘油激酶δ(DGKδ),在内质网中的住宅脂质激酶,触发从ER出口位点(ERES)的释放的含IFFT 88的囊泡,从而阐述了他们的运动到初级纤毛。由其突变最初涉及初级纤毛作为Shh信号传导场所的基因编码,已知IFFT 88是驱动纤毛内顺行运输的复合物B的一部分。我们发现,IFFT 88与DGKδ相互作用,并与ERES处的COPII包被囊泡相关。使用RNAi沉默和基因敲除策略的组合,我们进一步表明DGKδ是支持Shh信号在体外和体内所必需的,证明了这种调节的生理意义。
The morphogenic factor Sonic hedgehog (Shh) signals through the primary cilium, which relies on intraflagellar transport to maintain its structural integrity and function. However, the process by which protein and lipid cargos are delivered to the primary cilium from their sites of synthesis still remains poorly characterized. Here, we report that diacylglycerol kinase δ (DGKδ), a residential lipid kinase in the endoplasmic reticulum, triggers the release of IFT88-containing vesicles from the ER exit sites (ERES), thereby setting forth their movement to the primary cilium. Encoded by the gene whose mutations originally implicated the primary cilium as the venue of Shh signaling, IFT88 is known to be part of the complex B that drives the anterograde transport within cilia. We show that IFT88 interacts with DGKδ, and is associated with COPII-coated vesicles at the ERES. Using a combination of RNAi silencing and gene knockout strategies, we further show that DGKδ is required for supporting Shh signaling both in vitro and in vivo, demonstrating the physiological significance of this regulation.
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