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Modeling Paracrine Noncanonical Wnt Signaling In Vitro
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Canonical Wnt signaling induces focal adhesion and Integrin beta-1 endocytosis

Nydia Tejeda-Muñoz1, Marco Morselli2, Yuki Moriyama1,3

  • 1Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles 90095-1662, USA.

Iscience
|April 11, 2022
PubMed

Insights

Wnt signaling triggers the removal of Integrin β1 (ITGβ1) from cell surfaces, impacting focal adhesions and cellular structure. This interaction between Wnt and focal adhesion pathways affects cell biology and cancer.

Area of Science:

  • Cell Biology
  • Molecular Signaling
  • Biochemistry

Background:

  • Canonical Wnt signaling involves receptor complex sequestration within multivesicular bodies (MVBs).
  • Focal adhesions (FAs) and Integrins (like Integrin β1 or ITGβ1) connect the cytoskeleton to the extracellular matrix, crucial for cell adhesion and migration.

Purpose of the Study:

  • To investigate the effect of Wnt signaling on focal adhesion proteins and Integrin β1 localization.
  • To elucidate the relationship between Wnt-induced endocytosis and changes in the actin cytoskeleton.
  • To determine the functional consequence of ITGβ1 depletion on Wnt signaling.

Main Methods:

  • Utilized in situ protease protection assays in cultured cells to track ITGβ1 localization within MVBs.
  • Employed Xenopus embryos to study the in vivo effects of Wnt8 mRNA and ITGβ1 depletion on Wnt signaling.
  • Observed changes in the actin cytoskeleton and cell surface ITGβ1 levels upon Wnt stimulation.

Main Results:

  • Wnt signaling induces the endocytosis of focal adhesion proteins and depletes Integrin β1 (ITGβ1) from the cell surface.
  • ITGβ1 was found sequestered within Wnt-induced MVBs, alongside GSK3 and FA proteins.
  • Depletion of ITGβ1 in Xenopus embryos reduced Wnt signaling, indicating a functional link.

Conclusions:

  • Canonical Wnt signaling and focal adhesion pathways exhibit crosstalk.
  • Wnt-induced endocytosis of ITGβ1 impacts cellular structure and Wnt signaling itself.
  • This crosstalk has implications for understanding human cancer and fundamental cell biology.
Keywords:
Cell biologyDevelopmental biologyOmics

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