Pitchfork and Gprasp2 Target Smoothened to the Primary Cilium for Hedgehog Pathway Activation.
Pitchfork and Gprasp2 Target Smoothened to the Primary Cilium for Hedgehog Pathway Activation.
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DOI：
10.1371/journal.pone.0149477
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Lickert H
中科院分区：
文献类型：
--
作者：
Jung B;Padula D;Burtscher I;Landerer C;Lutter D;Theis F;Messias AC;Geerlof A;Sattler M;Kremmer E;Boldt K;Ueffing M;Lickert H
七跨膜受体平滑(Smo)通过转位到初级纤毛(PC)激活所有Hedgehog(HH)信号，但这是如何调节的还不是很清楚。在这里，我们表明Pitchfork(Pifo)和G蛋白偶联受体相关分类蛋白2(Gprasp2)是HH诱导的纤毛靶向复合体的重要组成部分，能够调节Smo向PC的转运。Pifo或Gprasp2的缺失导致Smo转位到PC的失败和HH靶基因的缺乏激活。总之，我们的结果确定了一种受HH信号调节的新的蛋白质复合体，它是纤毛运输和HH途径激活所必需的。
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.