May Scott R, Ashique Amir M, Karlen Mattias, Wang Baolin, Shen Yiguo, Zarbalis Kostantinos, Reiter Jeremy, Ericson Johan, Peterson Andrew S
Ernest Gallo Clinic and Research Center, Emeryville, CA 94608, USA.
Dev Biol. 2005 Nov 15;287(2):378-89. doi: 10.1016/j.ydbio.2005.08.050. Epub 2005 Oct 17.
Sonic Hedgehog (Shh) signals are transduced into nuclear ratios of Gli transcriptional activator versus repressor. The initial part of this process is accomplished by Shh acting through Patched (Ptc) to regulate Smoothened (Smo) activity. The mechanisms by which Ptc regulates Smo, and Smo activity is transduced to processing of Gli proteins remain unclear. Recently, a forward genetic approach in mice identified a role for intraflagellar transport (IFT) genes in Shh signal transduction, downstream of Patched (Ptc) and Rab23. Here, we show that the retrograde motor for IFT is required in the mouse for the phenotypic expression of both Gli activator and repressor function and for effective proteolytic processing of Gli3. Furthermore, we show that the localization of Smo to primary cilia is disrupted in mutants. These data indicate that primary cilia act as specialized signal transduction organelles required for coupling Smo activity to the biochemical processing of Gli3 protein.
音猬因子（Shh）信号被转化为Gli转录激活因子与阻遏因子的核比率。该过程的初始部分是通过Shh作用于patched（Ptc）来调节 smoothened（Smo）活性来完成的。Ptc调节Smo的机制以及Smo活性如何转化为Gli蛋白的加工过程仍不清楚。最近，在小鼠中采用正向遗传学方法确定了鞭毛内运输（IFT）基因在Shh信号转导中的作用，该作用在patched（Ptc）和Rab23的下游。在这里，我们表明IFT的逆向运动蛋白在小鼠中对于Gli激活因子和阻遏因子功能的表型表达以及Gli3的有效蛋白水解加工是必需的。此外，我们表明在突变体中Smo定位于初级纤毛的过程被破坏。这些数据表明初级纤毛作为专门的信号转导细胞器，是将Smo活性与Gli3蛋白的生化加工偶联所必需的。
