Language
English
Publication Date
1-22-2024
Journal
Development Cell
DOI
10.1016/j.devcel.2023.11.027
PMID
38154460
PMCID
PMC10872876
PubMedCentral® Posted Date
1-22-2025
PubMedCentral® Full Text Version
Author MSS
Abstract
WNT morphogens trigger signaling pathways fundamental for embryogenesis, regeneration, and cancer. WNTs are modified with palmitoleate, which is critical for binding Frizzled (FZD) receptors and activating signaling. However, it is unknown how WNTs are released and spread from cells, given their strong lipid-dependent membrane attachment. We demonstrate that secreted FZD-related proteins and WNT inhibitory factor 1 are WNT carriers, potently releasing lipidated WNTs and forming active soluble complexes. WNT release occurs by direct handoff from the membrane protein WNTLESS to the carriers. In turn, carriers donate WNTs to glypicans and FZDs involved in WNT reception and to the NOTUM hydrolase, which antagonizes WNTs by lipid moiety removal. WNT transfer from carriers to FZDs is greatly facilitated by glypicans that serve as essential co-receptors in Wnt signaling. Thus, an extracellular network of carriers dynamically controls secretion, posttranslational regulation, and delivery of WNT morphogens, with important practical implications for regenerative medicine.
Keywords
Wnt Proteins, Glypicans, Wnt Signaling Pathway, Embryonic Development, Lipids, Frizzled Receptors, signaling, morphogen, WNT, receptor, lipids, extracellular
Published Open-Access
yes
Recommended Citation
de Almeida Magalhaes, Taciani; Liu, Jingjing; Chan, Charlene; et al., "Extracellular Carriers Control Lipid-Dependent Secretion, Delivery, and Activity of WNT Morphogens" (2024). Faculty and Staff Publications. 4876.
https://digitalcommons.library.tmc.edu/baylor_docs/4876
Graphical Abstract
Included in
Health Services Research Commons, Medical Cell Biology Commons, Medical Molecular Biology Commons, Medical Specialties Commons, Microbiology Commons