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 prote¬in 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.
Data availability
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The exon junction complex regulates the splicing of cell polarity gene dlg1 to control Wingless signaling in developmentPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE81220).
Article and author information
Author details
Funding
State Key Laboratory of Membrane Biology of the People's Republic of China (Grant)
- Alan Jian Zhu
Peking-Tsinghua Center for Life Sciences (Grant)
- Cheng Li
- Alan Jian Zhu
Ministry of Science and Technology of the People's Republic of China (2014CB942804)
- Alan Jian Zhu
National Science Foundation of the People's Republic of China (31371410)
- Alan Jian Zhu
National Science Foundation of the People's Republic of China (31401241)
- Min Liu
China Postdoctoral Science Foundation (Postdoctoral Fellowship, 2014M550556)
- Min Liu
Peking-Tsinghua Center for Life Sciences (Postdoctoral Fellowship)
- Min Liu
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Duojia Pan, UT Southwestern Medical Center, United States
Version history
- Received: April 24, 2016
- Accepted: August 14, 2016
- Accepted Manuscript published: August 18, 2016 (version 1)
- Version of Record published: September 1, 2016 (version 2)
Copyright
© 2016, Liu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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