Transduction of the Hedgehog signal through the dimerization of Fused and the nuclear translocation of Cubitus interruptus  

作　　者：Yanyan Zhang Feifei Mao Yi Lu Wenqing Wu Lei Zhang Yun Zhao 

机构地区：[1]State Key Laboratory of Cell Biology, institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chi- nese Academy of Sciences, Shanghai 200031, China

出　　处：《Cell Research》2011年第10期1436-1451,共16页细胞研究（英文版）

基　　金：We thank Dr Jin Jiang （University of Texas Southwestern Medical Center at Dallas, USA）, Dr Robert Holmgren （Northwestern University, USA）, the ARIAD Pharmaceuticals and Developmental Studies Hybridoma Bank at the university of Iowa for reagents. We thank Dr Xiaochen Wang （National Institute of Biological Sciences, China）, Dr Min Wu （Wuhan University, China） and Dr Zhaocai Zhou （Institute of Biochemistry and Cell Biology, CAS, China） for critical comments on the manuscript. This work was supported by grants from the National Natural Science Foundation of China （30623003, 30971647 and 30971646）, the National Key Scientific Program of China （2011 CB943902 and 2010CB912100）, Shanghai Pujiang Program （09PJ1410900） and also from the ＂Strategic Priority Research Program＂ of the Chinese Academy of Sciences （XDA01010405 and XDA01010406）. Y Z and L Z are the scholars of the Hundred Talents Program of the Chinese Academy of Sciences.

摘　　要：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 dimeriza- tion. Dimerized Fu is phosphorylated and transduees 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.

关 键 词：Cubitus interruptus DROSOPHILA FUSED HEDGEHOG MORPHOGEN 

分 类 号：Q257[生物学—细胞生物学] Q513