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叉状蛋白和Gprasp2将平滑蛋白靶向初级纤毛以激活刺猬信号通路。

Pitchfork and Gprasp2 Target Smoothened to the Primary Cilium for Hedgehog Pathway Activation.

作者信息

Jung Bomi, Padula Daniela, Burtscher Ingo, Landerer Cedric, Lutter Dominik, Theis Fabian, Messias Ana C, Geerlof Arie, Sattler Michael, Kremmer Elisabeth, Boldt Karsten, Ueffing Marius, Lickert Heiko

机构信息

Institute of Diabetes and Regeneration Research, Helmholtz Zentrum München, München-Neuherberg, Germany.

Institute of Stem Cell Research, Helmholtz Zentrum München, München-Neuherberg, Germany.

出版信息

PLoS One. 2016 Feb 22;11(2):e0149477. doi: 10.1371/journal.pone.0149477. eCollection 2016.

DOI:10.1371/journal.pone.0149477
PMID:26901434
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4763541/
Abstract

The seven-transmembrane receptor Smoothened (Smo) activates all Hedgehog (Hh) signaling by translocation into the primary cilia (PC), but how this is regulated is not well understood. Here we show that Pitchfork (Pifo) and the G protein-coupled receptor associated sorting protein 2 (Gprasp2) are essential components of an Hh induced ciliary targeting complex able to regulate Smo translocation to the PC. Depletion of Pifo or Gprasp2 leads to failure of Smo translocation to the PC and lack of Hh target gene activation. Together, our results identify a novel protein complex that is regulated by Hh signaling and required for Smo ciliary trafficking and Hh pathway activation.

摘要

七次跨膜受体Smo（平滑蛋白）通过转运至初级纤毛（PC）来激活所有的刺猬信号通路（Hh），但其调控机制尚不清楚。我们在此表明，叉状蛋白（Pifo）和G蛋白偶联受体相关分选蛋白2（Gprasp2）是Hh诱导的纤毛靶向复合物的重要组成部分，该复合物能够调节Smo转运至PC。Pifo或Gprasp2的缺失会导致Smo无法转运至PC，且Hh靶基因无法激活。总之，我们的研究结果鉴定出一种由Hh信号通路调控的新型蛋白复合物，它是Smo纤毛运输和Hh信号通路激活所必需的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39b9/4763541/24fa98ce9940/pone.0149477.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39b9/4763541/edaf100ab822/pone.0149477.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39b9/4763541/459c33aec5b7/pone.0149477.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39b9/4763541/61ffe95d33a1/pone.0149477.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39b9/4763541/8922ebca043f/pone.0149477.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39b9/4763541/0cda59be3ac8/pone.0149477.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39b9/4763541/785b925b6d6d/pone.0149477.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39b9/4763541/24fa98ce9940/pone.0149477.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39b9/4763541/edaf100ab822/pone.0149477.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39b9/4763541/459c33aec5b7/pone.0149477.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39b9/4763541/61ffe95d33a1/pone.0149477.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39b9/4763541/8922ebca043f/pone.0149477.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39b9/4763541/0cda59be3ac8/pone.0149477.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39b9/4763541/785b925b6d6d/pone.0149477.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39b9/4763541/24fa98ce9940/pone.0149477.g007.jpg

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