Transduction of the Hedgehog signal through the dimerization of Fused and the nuclear translocation of Cubitus interruptus.
Transduction of the Hedgehog signal through the dimerization of Fused and the nuclear translocation of Cubitus interruptus.
复制标题
通过 Fused 的二聚化和 Cubitus Interruptus 的核转位来转导 Hedgehog 信号
作者：
Hedgehog（Hh）家族的分泌蛋白对于脊椎动物和无脊椎动物的发育都是必不可少的。Smoothened（Smo）是后生动物发育过程中的主要形态原之一，通过其胞质尾区的差异磷酸化，将Hh信号传递到细胞膜上，激活信号通路，导致靶基因的差异表达。然而，Smo如何通过Costal 2（Cos 2）/Fused（Fu）复合物转导分级Hh信号仍然知之甚少。在这里，我们提出了一个模型的细胞响应Hh梯度通过翻译Smo磷酸化信息Fu二聚化和Cubitus interruptus（Ci）核定位信息。我们的研究结果表明，Smo的磷酸化的C-末端招募Cos 2/Fu复合物的膜通过Smo和Cos 2之间的相互作用，这进一步诱导Fu二聚化。二聚化Fu被磷酸化，并通过磷酸化Cos 2和Fu抑制因子（Su（fu））转导Hh信号。我们进一步表明，这一过程促进了全长Ci（Ci 155）和Cos 2或Su（fu）的解离，并导致Ci 155易位到细胞核中，激活靶基因的表达。
The Hedgehog (Hh) family of secreted proteins is essential for development in both vertebrates and invertebrates. As one of main morphogens during metazoan development, the graded Hh signal is transduced across the plasma membrane by Smoothened (Smo) through the differential phosphorylation of its cytoplasmic tail, leading to pathway activation and the differential expression of target genes. However, how Smo transduces the graded Hh signal via the Costal2 (Cos2)/Fused (Fu) complex remains poorly understood. Here we present a model of the cell response to a Hh gradient by translating Smo phosphorylation information to Fu dimerization and Cubitus interruptus (Ci) nuclear localization information. Our findings suggest that the phosphorylated C-terminus of Smo recruits the Cos2/Fu complex to the membrane through the interaction between Smo and Cos2, which further induces Fu dimerization. Dimerized Fu is phosphorylated and transduces the Hh signal by phosphorylating Cos2 and Suppressor of Fu (Su (fu)). We further show that this process promotes the dissociation of the full-length Ci (Ci155) and Cos2 or Su (fu), and results in the translocation of Ci155 into the nucleus, activating the expression of target genes.
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