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

被引:15
作者
Johansson, Marie [1 ,2 ]
Giger, Florence A. [1 ,2 ]
Fielding, Triona [1 ,2 ]
Houart, Corinne [1 ,2 ]
机构
[1] Kings Coll London, Inst Psychiat Psychol & Neurosci, Ctr Dev Neurobiol, London SE1 1UL, England
[2] Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC Ctr Neurodev Disorders, London SE1 1UL, England
基金
英国生物技术与生命科学研究理事会; 英国医学研究理事会;
关键词
E-CADHERIN; CONVERGENT EXTENSION; WNT; BINDING; DICKKOPF-1; EXPRESSION; MIGRATION; DOMAIN; GENES; LRP6;
D O I
10.1016/j.devcel.2019.10.026
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 beta-catenin protein degradation. Concurrently, Dkk1 prevents nuclear localization of beta-catenin by restricting its distribution to a discrete submembrane pool. We propose that redistribution of cytosolic beta-catenin by Dkk1 concomitantly drives repression of cell adhesion and inhibits beta-catenin-dependent transcriptional output.
引用
收藏
页码:775 / +
页数:15
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