The Hedgehog pathway, critical to vertebrate development, is organized in primary cilia. Activation of signaling causes the Hedgehog receptor Ptch1 to exit cilia, allowing a second receptor, Smo, to accumulate in cilia and activate the downstream steps of the pathway. Mechanisms regulating the dynamics of these receptors are unknown, but the ubiquitination of Smo regulates its interaction with the intraflagellar transport system to control ciliary levels. A focused screen of ubiquitin-related genes identified nine required for maintaining low ciliary Smo at the basal state. These included cytoplasmic E3s (Arih2, Mgrn1, and Maea), a ciliary localized E3 (Wwp1), a ciliary localized E2 (Ube2l3), a deubiquitinase (Bap1), and three adaptors (Kctd5, Skp1a, and Skp2). The ciliary E3, Wwp1, binds Ptch1 and localizes to cilia at the basal state. Activation of signaling removes both Ptch1 and Wwp1 from cilia, thus providing an elegant mechanism for Ptch1 to regulate ciliary Smo levels.

中文翻译：

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E3泛素连接酶Wwp1调节Hedgehog受体的纤毛动力学 Smoothened

对脊椎动物发育至关重要的刺猬通路是在初级纤毛中组织的。信号传导的激活导致 Hedgehog 受体 Ptch1 退出纤毛，从而允许第二个受体 Smo 在纤毛中积累并激活该通路的下游步骤。调节这些受体动态的机制尚不清楚，但 Smo 的泛素化调节其与鞭毛内运输系统的相互作用，以控制纤毛水平。对泛素相关基因的集中筛选确定了维持低纤毛 Smo 处于基础状态所需的 9 个基因。这些包括细胞质 E3（Arih2、Mgrn1 和 Maea）、纤毛定位 E3 (Wwp1)、纤毛定位 E2 (Ube2l3)、去泛素酶 (Bap1) 和三个接头（Kctd5、Skp1a 和 Skp2）。纤毛 E3，Wwp1，结合 Ptch1 并定位于基底状态的纤毛。信号传导的激活会从纤毛中去除 Ptch1 和 Wwp1，从而为 Ptch1 调节纤毛 Smo 水平提供了一种优雅的机制。