Lateral transport of Smoothened from the plasma membrane to the membrane of the cilium.

Lateral transport of Smoothened from the plasma membrane to the membrane of the cilium.
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DOI:
10.1083/jcb.200907126
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发表时间:
2009-11-02
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Rohatgi R
Rohatgi R
中科院分区:
其他
文献类型:
--
作者:
Milenkovic L;Scott MP;Rohatgi R

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描述了配体刺激的刺猬蛋白平滑横向运输进入纤毛的独特途径。初级纤毛的功能主要取决于特定蛋白质在纤毛膜中的定位。该领域的一个主要挑战是了解纤毛的蛋白质运输。 Hedgehog (Hh) 途径蛋白 Smoothened (Smo) 是一种 7 次跨膜蛋白,当接收到配体时,它会移动到纤毛。使用基于显微镜的脉冲追踪分析,我们发现 Smo 通过横向运输路径从质膜移动到睫状膜。通过扩散或主动运输的横向运动与目前研究的哺乳动物纤毛蛋白运输途径截然不同,后者强调将高尔基体衍生的囊泡定向运输到纤毛基部。我们预计这种替代途径将被在纤毛上起作用的其他信号蛋白使用。 Smo 所采取的途径可能会为在癌症和再生中调节 Hh 信号传导提供新的策略。
A distinct pathway for ligand-stimulated lateral trafficking of the hedgehog protein Smoothened into cilia is described. The function of primary cilia depends critically on the localization of specific proteins in the ciliary membrane. A major challenge in the field is to understand protein trafficking to cilia. The Hedgehog (Hh) pathway protein Smoothened (Smo), a 7-pass transmembrane protein, moves to cilia when a ligand is received. Using microscopy-based pulse-chase analysis, we find that Smo moves through a lateral transport pathway from the plasma membrane to the ciliary membrane. Lateral movement, either via diffusion or active transport, is quite distinct from currently studied pathways of ciliary protein transport in mammals, which emphasize directed trafficking of Golgi-derived vesicles to the base of the cilium. We anticipate that this alternative route will be used by other signaling proteins that function at cilia. The path taken by Smo may allow novel strategies for modulation of Hh signaling in cancer and regeneration.
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