The primary cilium as a Hedgehog signal transduction machine.
The primary cilium as a Hedgehog signal transduction machine.
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DOI：
10.1016/s0091-679x(08)94010-3
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发表时间：
2009
影响因子：
--
通讯作者：
Anderson, Kathryn V.
中科院分区：
文献类型：
--
作者：
Goetz, Sarah C.;Ocbina, Polloneal J. R.;Anderson, Kathryn V.
Hedgehog（Hh）信号转导通路对于许多器官系统的发育和模式化是必不可少的，并且在多种人类癌症中具有重要作用。对小鼠胚胎模式突变体的遗传筛选首先显示了哺乳动物Hh信号传导和鞭毛内转运（IFT）之间的联系，IFT是构建初级纤毛所需的过程，初级纤毛是大多数脊椎动物细胞上发现的小细胞突起。另外的遗传和细胞生物学研究提供了非常有力的证据，哺乳动物Hh信号依赖于初级纤毛。在这里，我们回顾的证据，定义的整体作用，IFT蛋白和纤毛在调节Hh信号转导通路在脊椎动物中发挥作用。我们讨论了控制Hh途径蛋白定位于纤毛的机制，重点是跨膜蛋白Smoothened，它响应Hh配体而进入纤毛。由纤毛相关蛋白的损失引起的表型是复杂的，这表明纤毛和IFT在介导Hh信号传导中起着积极的作用，而不是简单地作为一个腔室，其中通路组分被集中。果蝇中的刺猬信号不依赖于纤毛，但纤毛和Hh通路的组成部分之间似乎存在古老的联系，这可能揭示了果蝇和哺乳动物Hh通路之间的根本差异是如何在进化中出现的。
The Hedgehog (Hh) signal transduction pathway is essential for the development and patterning of numerous organ systems, and has important roles in a variety of human cancers. Genetic screens for mouse embryonic patterning mutants first showed a connection between mammalian Hh signaling and intraflagellar transport (IFT), a process required for construction of the primary cilium, a small cellular projection found on most vertebrate cells. Additional genetic and cell biological studies have provided very strong evidence that mammalian Hh signaling depends on the primary cilium. Here, we review the evidence that defines the integral roles that IFT proteins and cilia play in the regulation the Hh signal transduction pathway in vertebrates. We discuss the mechanisms that control localization of Hh pathway proteins to the cilium, focusing on the transmembrane protein Smoothened, which moves into the cilium in response to Hh ligand. The phenotypes caused by loss of cilia-associated proteins are complex, which suggests that cilia and IFT play active roles in mediating Hh signaling rather than serving simply as a compartment in which pathway components are concentrated. Hedgehog signaling in Drosophila does not depend on cilia, but there appear to be ancient links between cilia and components of the Hh pathway that may reveal how this fundamental difference between the Drosophila and mammalian Hh pathways arose in evolution.