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Destruction complex dynamics: Wnt/β-catenin signaling alters Axin-GSK3β interactions in vivo

Daniel B Lybrand1,2, Misha Naiman1,2, Jessie May Laumann1

  • 1Dept. of Integrative Biosciences, School of Dentistry, Oregon Health and Science University, Portland, OR 97239, USA.

Development (Cambridge, England)
|June 14, 2019
PubMed

Insights

Researchers visualized the Axin/APC/GSK3β destruction complex (DC) in vivo, revealing how Wnt signaling inactivates it to allow β-catenin to activate gene transcription.

Area of Science:

  • Cell Biology
  • Developmental Biology
  • Molecular Biology

Background:

  • The Wnt/β-catenin pathway is crucial for development and disease.
  • The Axin/APC/GSK3β destruction complex (DC) normally degrades β-catenin.
  • Mechanisms of DC regulation by Wnt signaling in vivo remain unclear.

Purpose of the Study:

  • To visualize and analyze the Wnt/β-catenin destruction complex (DC) in vivo.
  • To elucidate the dynamic regulation of the DC during Wnt signaling.
  • To understand how Wnt pathway activation prevents β-catenin degradation.

Main Methods:

  • Utilized bimolecular fluorescence complementation (BiFC) in Drosophila.
  • Focused on Wnt/Wg signaling patterns in the developing Drosophila wing.
  • Observed DC activity under near-physiological conditions.

Main Results:

  • Defined the sequence of events in DC inactivation upon Wnt receptor activation.
  • Showed Wnt signaling induces conformational changes in the DC, altering Axin-GSK3β interactions.
  • Found active DCs surrounding the nucleus, controlling β-catenin degradation and nuclear access.
  • Demonstrated DC inactivation and removal upon Wnt signal transduction.

Conclusions:

  • Proposed a novel mechanistic model for dynamic Wnt signal transduction in vivo.
  • Highlighted the role of DC conformational changes in Wnt pathway regulation.
  • Emphasized the spatial regulation of β-catenin by DCs near the nucleus.
Keywords:
AxinDestruction complexDrosophilaGSK3Wnt signalingβ-Catenin

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