PUBLICATION

Dkk1 Controls Cell-Cell Interaction through Regulation of Non-nuclear β-Catenin Pools

Authors
Johansson, M., Giger, F.A., Fielding, T., Houart, C.
ID
ZDB-PUB-191202-3
Date
2019
Source
Developmental Cell   51(6): 775-786.e3 (Journal)
Registered Authors
Houart, Corinne, Johansson, Marie
Keywords
Dickkopf-1, Dkk1, Wnt signaling morphogenesis, cell adhesion, cell migration, metastasis, neurodegeneration, polarity, β-catenin
MeSH Terms
  • Animals
  • Cell Communication/physiology*
  • Cell Movement/physiology
  • Intercellular Signaling Peptides and Proteins/metabolism*
  • Wnt Proteins/metabolism
  • Wnt Signaling Pathway/physiology*
  • Zebrafish
  • Zebrafish Proteins/metabolism*
  • beta Catenin/metabolism*
PubMed
31786070 Full text @ Dev. Cell
Abstract
Dickkopf-1 (Dkk1) is a secreted Wnt antagonist with a well-established role in head induction during development. Numerous studies have emerged implicating Dkk1 in various malignancies and neurodegenerative diseases through an unknown mechanism. Using zebrafish gastrulation as a model for collective cell migration, we unveil such a mechanism, identifying a role for Dkk1 in control of cell connectivity and polarity in vivo, independent of its known function. We find that Dkk1 localizes to adhesion complexes at the plasma membrane and regions of concentrated actomyosin, suggesting a direct involvement in regulation of local cell adhesion. Our results show that Dkk1 represses cell polarization and integrity of cell-cell adhesion, independently of its impact on β-catenin protein degradation. Concurrently, Dkk1 prevents nuclear localization of β-catenin by restricting its distribution to a discrete submembrane pool. We propose that redistribution of cytosolic β-catenin by Dkk1 concomitantly drives repression of cell adhesion and inhibits β-catenin-dependent transcriptional output.
Genes / Markers
Figures
Figure Gallery
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Errata and Notes