title: The exon junction complex regulates the splicing of cell polarity gene dlg1 to control Wingless signaling in development.
abstract: 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.
authors.affiliation: State Key Laboratory of Membrane Biology and Minstry of Education Key Laboratory of Cell Proliferation and Differentiation, Peking University, Beijing, China.|School of Life Sciences, Peking University, Beijing, China.|Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisplinary Studies, Peking University, Beijing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Membrane Biology and Minstry of Education Key Laboratory of Cell Proliferation and Differentiation, Peking University, Beijing, China.|School of Life Sciences, Peking University, Beijing, China.
authors.forename: Yajuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Membrane Biology and Minstry of Education Key Laboratory of Cell Proliferation and Differentiation, Peking University, Beijing, China.|School of Life Sciences, Peking University, Beijing, China.|Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisplinary Studies, Peking University, Beijing, China.
authors.forename: Aiguo
authors.initials: A
authors.lastname: Liu
authors.affiliation: School of Life Sciences, Peking University, Beijing, China.|Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisplinary Studies, Peking University, Beijing, China.|Center for Bioinformatics, Peking University, Beijing, China.|Center for Statistical Science, Peking University, Beijing, China.
authors.forename: Ruifeng
authors.initials: R
authors.lastname: Li
authors.affiliation: School of Life Sciences, Peking University, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Su
authors.affiliation: State Key Laboratory of Membrane Biology and Minstry of Education Key Laboratory of Cell Proliferation and Differentiation, Peking University, Beijing, China.|School of Life Sciences, Peking University, Beijing, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Du
authors.affiliation: School of Life Sciences, Peking University, Beijing, China.|Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisplinary Studies, Peking University, Beijing, China.|Center for Bioinformatics, Peking University, Beijing, China.|Center for Statistical Science, Peking University, Beijing, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Li
authors.affiliation: State Key Laboratory of Membrane Biology and Minstry of Education Key Laboratory of Cell Proliferation and Differentiation, Peking University, Beijing, China.|School of Life Sciences, Peking University, Beijing, China.|Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisplinary Studies, Peking University, Beijing, China.
authors.forename: Alan Jian
authors.identifier: 0000-0001-8208-1729
authors.initials: AJ
authors.lastname: Zhu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000074288:Discs Large Homolog 1 Protein; D000072261:Dishevelled Proteins / Q000378:metabolism*; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D008565:Membrane Proteins; D012326:RNA Splicing; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics*; D060449:Wnt Signaling Pathway; D051155:Wnt1 Protein / Q000096:biosynthesis*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C513314:DLG1 protein, human; C000606578:DVL1 protein, human; D000074288:Discs Large Homolog 1 Protein; D000072261:Dishevelled Proteins; D029721:Drosophila Proteins; D008565:Membrane Proteins; D025521:Tumor Suppressor Proteins; D051155:Wnt1 Protein; C000606588:dsh protein, Drosophila; C074622:wg protein, Drosophila; C070350:dlg1 protein, Drosophila
keywords: D. melanogaster; Dishevelled; RNA splicing; Wnt/Wingless signaling; cell biology; developmental biology; discs large; exon junction complex; stem cells