TY - JOUR TI - The exon junction complex regulates the splicing of cell polarity gene dlg1 to control Wingless signaling in development AU - Liu, Min AU - Li, Yajuan AU - Liu, Aiguo AU - Li, Ruifeng AU - Su, Ying AU - Du, Juan AU - Li, Cheng AU - Zhu, Alan Jian A2 - Pan, Duojia VL - 5 PY - 2016 DA - 2016/08/18 SP - e17200 C1 - eLife 2016;5:e17200 DO - 10.7554/eLife.17200 UR - https://doi.org/10.7554/eLife.17200 AB - Wingless (Wg)/Wnt signaling is conserved in all metazoan animals and plays critical roles in development. The Wg/Wnt morphogen reception is essential for signal activation, whose activity is mediated through the receptor complex and a scaffold protein Dishevelled (Dsh). We report here that the exon junction complex (EJC) activity is indispensable for Wg signaling by maintaining an appropriate level of Dsh protein for Wg ligand reception in Drosophila. Transcriptome analyses in Drosophila wing imaginal discs indicate that the EJC controls the splicing of the cell polarity gene discs large 1 (dlg1), whose coding protein directly interacts with Dsh. Genetic and biochemical experiments demonstrate that Dlg1 protein acts independently from its role in cell polarity to protect Dsh protein from lysosomal degradation. More importantly, human orthologous Dlg protein is sufficient to promote Dvl protein stabilization and Wnt signaling activity, thus revealing a conserved regulatory mechanism of Wg/Wnt signaling by Dlg and EJC. KW - discs large KW - Dishevelled KW - exon junction complex KW - RNA splicing KW - Wnt/Wingless signaling JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -