Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Dev Cell. 2012 May 15;22(5):940-51. doi: 10.1016/j.devcel.2012.04.009.
The intraflagellar transport (IFT) system is required for building primary cilia, sensory organelles that cells use to respond to their environment. IFT particles are composed of about 20 proteins, and these proteins are highly conserved across ciliated species. IFT25, however, is absent from some ciliated organisms, suggesting that it may have a unique role distinct from ciliogenesis. Here, we generate an Ift25 null mouse and show that IFT25 is not required for ciliary assembly but is required for proper Hedgehog signaling, which in mammals occurs within cilia. Mutant mice die at birth with multiple phenotypes, indicative of Hedgehog signaling dysfunction. Cilia lacking IFT25 have defects in the signal-dependent transport of multiple Hedgehog components including Patched-1, Smoothened, and Gli2, and fail to activate the pathway upon stimulation. Thus, IFT function is not restricted to building cilia where signaling occurs, but also plays a separable role in signal transduction events.
鞭毛内运输（IFT）系统对于构建初级纤毛是必需的，初级纤毛是细胞用来感知环境的感觉器官。IFT 颗粒由大约 20 种蛋白质组成，这些蛋白质在纤毛物种中高度保守。然而，IFT25 缺失于一些纤毛生物中，这表明它可能具有不同于纤毛发生的独特作用。在这里，我们生成了一个 Ift25 缺失的小鼠，并表明 IFT25 对于纤毛组装不是必需的，但对于 Hedgehog 信号传导是必需的，在哺乳动物中，Hedgehog 信号传导发生在纤毛内。突变小鼠在出生时死亡，具有多种表型，表明 Hedgehog 信号传导功能障碍。缺乏 IFT25 的纤毛在信号依赖性运输多个 Hedgehog 成分（包括 Patched-1、Smoothened 和 Gli2）方面存在缺陷，并且在受到刺激时无法激活该途径。因此，IFT 功能不仅限于发生信号的纤毛构建，而且在信号转导事件中还发挥可分离的作用。
