Smoothened transduces Hedgehog signal by physically interacting with Costal2/Fused complex through its C-terminal tail
Smoothened transduces Hedgehog signal by physically interacting with Costal2/Fused complex through its C-terminal tail
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DOI：
10.1101/gad.1136603
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发表时间：
2003-11-01
影响因子：
10.5
通讯作者：
Jiang, J
中科院分区：
文献类型：
--
作者：
Jia, JH;Tong, C;Jiang, J
Hedgehog（Hh）家族分泌蛋白控制动物发育中生长和模式化的许多方面。七跨膜蛋白Smoothened（Smo）在脊椎动物和无脊椎动物中转导Hh信号;然而，其作用机制仍然未知。我们发现，Smo缺乏其C-末端尾（C-尾）是无活性的，而膜栓系的Smo C-尾具有组成性的Hh信号传导活性，尽管水平较低。Smo通过其C-尾与Costal 2（Cos 2）和Fused（Fu）物理相互作用。从Smo中删除Cos 2/Fu结合结构域可消除其信号传导活性。此外，过表达Cos 2突变体无法结合Fu和Ci，但保留了Smo结合活性，从而阻断了Hh信号传导。两者合计，我们的研究结果表明，Smo通过与Cos 2/Fu蛋白复合物的物理相互作用来转导Hh信号。
The Hedgehog (Hh) family of secreted proteins controls many aspects of growth and patterning in animal development. The seven-transmembrane protein Smoothened (Smo) transduces the Hh signal in both vertebrates and invertebrates; however, the mechanism of its action remains unknown. We found that Smo lacking its C-terminal tail (C-tail) is inactive, whereas membrane-tethered Smo C-tail has constitutive albeit low levels of Hh signaling activity. Smo physically interacts with Costal2 (Cos2) and Fused (Fu) through its C-tail. Deletion of the Cos2/Fu-binding domain from Smo abolishes its signaling activity. Moreover, overexpressing Cos2 mutants that fail to bind Fu and Ci but retain Smo-binding activity blocks Hh signaling. Taken together, our results suggest that Smo transduces the Hh signal by physically interacting with the Cos2/Fu protein complex.