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The exon junction complex regulates the splicing of cell polarity gene dlg1 to control Wingless signaling in

Min Liu1,2,3, Yajuan Li1,2, Aiguo Liu1,2,3

  • 1State Key Laboratory of Membrane Biology and Minstry of Education Key Laboratory of Cell Proliferation and Differentiation, Peking University, Beijing, China.

Elife
|August 19, 2016
PubMed

Insights

The exon junction complex (EJC) is essential for Wingless (Wg) signaling by regulating Dishevelled (Dsh) protein levels. This regulation involves the splicing of discs large 1 (Dlg1), which stabilizes Dsh and is conserved in humans.

Area of Science:

  • Developmental Biology
  • Molecular Cell Biology
  • Genetics

Background:

  • Wingless (Wg)/Wnt signaling is a conserved pathway crucial for metazoan development.
  • Signal activation relies on morphogen reception via a receptor complex and the scaffold protein Dishevelled (Dsh).

Purpose of the Study:

  • To investigate the role of the exon junction complex (EJC) in Wg signaling.
  • To elucidate the mechanism by which EJC influences Wg signaling components.

Main Methods:

  • Transcriptome analysis in Drosophila wing imaginal discs.
  • Genetic and biochemical experiments in Drosophila.
  • Functional assays using human orthologous proteins.

Main Results:

  • EJC activity is indispensable for Wg signaling in Drosophila.
  • EJC controls the splicing of the cell polarity gene discs large 1 (dlg1).
  • Dlg1 protein stabilizes Dsh protein by preventing lysosomal degradation, independent of its cell polarity function.
  • Human Dlg protein can stabilize Dvl protein and enhance Wnt signaling.

Conclusions:

  • EJC maintains Dsh protein levels, crucial for Wg ligand reception.
  • Dlg1 acts as a conserved regulator of Dsh protein stability.
  • This study reveals a conserved mechanism linking EJC, Dlg, and Wnt signaling pathway regulation.
Keywords:
D. melanogasterDishevelledRNA splicingWnt/Wingless signalingcell biologydevelopmental biologydiscs largeexon junction complexstem cells

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