β-catenin-mediated Wnt signal transduction proceeds through an endocytosis-independent mechanism.

Titleβ-catenin-mediated Wnt signal transduction proceeds through an endocytosis-independent mechanism.
Publication TypeJournal Article
Year of Publication2020
AuthorsRim EY, Kinney LK, Nusse R
JournalMolecular biology of the cell
Volume31
Issue13
Pagination1425-1436
Date Published2020 Jun 15
ISSN1059-1524
AbstractThe Wnt pathway is a key intercellular signaling cascade that regulates development, tissue homeostasis, and regeneration. However, gaps remain in our understanding of the molecular events that take place between ligand-receptor binding and target gene transcription. We used a novel tool for quantitative, real-time assessment of endogenous pathway activation, measured in single cells, to answer an unresolved question in the field-whether receptor endocytosis is required for Wnt signal transduction. We combined knockdown or knockout of essential components of clathrin-mediated endocytosis with quantitative assessment of Wnt signal transduction in mouse embryonic stem cells (mESCs). Disruption of clathrin-mediated endocytosis did not affect accumulation and nuclear translocation of β-catenin, as measured by single-cell live imaging of endogenous β-catenin, and subsequent target gene transcription. Disruption of another receptor endocytosis pathway, caveolin-mediated endocytosis, did not affect Wnt pathway activation in mESCs. Additional results in multiple cell lines support that endocytosis is not a requirement for Wnt signal transduction. We show that off-target effects of a drug used to inhibit endocytosis may be one source of the discrepancy among reports on the role of endocytosis in Wnt signaling.
URLhttps://www.molbiolcell.org/doi/full/10.1091/mbc.E20-02-0114?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed
DOI10.1091/mbc.E20-02-0114
Short TitleMol Biol Cell