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

Abstract 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 synthesi...

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Autores principales: Jie Ding, Lei Shao, Yixing Yao, Xin Tong, Huaize Liu, Shen Yue, Lu Xie, Steven Y. Cheng
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/e5210e7b77f24980b5cd040dcfcd662c
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spelling oai:doaj.org-article:e5210e7b77f24980b5cd040dcfcd662c2021-12-02T11:40:20ZDGKδ triggers endoplasmic reticulum release of IFT88-containing vesicles destined for the assembly of primary cilia10.1038/s41598-017-05680-82045-2322https://doaj.org/article/e5210e7b77f24980b5cd040dcfcd662c2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05680-8https://doaj.org/toc/2045-2322Abstract 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.Jie DingLei ShaoYixing YaoXin TongHuaize LiuShen YueLu XieSteven Y. ChengNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Jie Ding
Lei Shao
Yixing Yao
Xin Tong
Huaize Liu
Shen Yue
Lu Xie
Steven Y. Cheng
DGKδ triggers endoplasmic reticulum release of IFT88-containing vesicles destined for the assembly of primary cilia
description Abstract 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.
format article
author Jie Ding
Lei Shao
Yixing Yao
Xin Tong
Huaize Liu
Shen Yue
Lu Xie
Steven Y. Cheng
author_facet Jie Ding
Lei Shao
Yixing Yao
Xin Tong
Huaize Liu
Shen Yue
Lu Xie
Steven Y. Cheng
author_sort Jie Ding
title DGKδ triggers endoplasmic reticulum release of IFT88-containing vesicles destined for the assembly of primary cilia
title_short DGKδ triggers endoplasmic reticulum release of IFT88-containing vesicles destined for the assembly of primary cilia
title_full DGKδ triggers endoplasmic reticulum release of IFT88-containing vesicles destined for the assembly of primary cilia
title_fullStr DGKδ triggers endoplasmic reticulum release of IFT88-containing vesicles destined for the assembly of primary cilia
title_full_unstemmed DGKδ triggers endoplasmic reticulum release of IFT88-containing vesicles destined for the assembly of primary cilia
title_sort dgkδ triggers endoplasmic reticulum release of ift88-containing vesicles destined for the assembly of primary cilia
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/e5210e7b77f24980b5cd040dcfcd662c
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