PUBLICATION
In Situ Fucosylation of the Wnt Co-receptor LRP6 Increases Its Endocytosis and Reduces Wnt/β-Catenin Signaling
- Authors
- Hong, S., Feng, L., Yang, Y., Jiang, H., Hou, X., Guo, P., Marlow, F.L., Stanley, P., Wu, P.
- ID
- ZDB-PUB-210702-16
- Date
- 2020
- Source
- Cell chemical biology 27: 1140-1150.e4 (Journal)
- Registered Authors
- Marlow, Florence
- Keywords
- (1?3)-fucosylation, LRP6, Wnt signaling/?-catenin signaling, endocytosis
- MeSH Terms
-
- Animals
- CHO Cells
- Cricetinae
- Membrane Microdomains/metabolism
- Wnt Signaling Pathway*
- Monosaccharide Transport Proteins/genetics
- Monosaccharide Transport Proteins/metabolism
- Cricetulus
- Fucose/metabolism*
- Fucose/pharmacology
- Low Density Lipoprotein Receptor-Related Protein-6/genetics
- Low Density Lipoprotein Receptor-Related Protein-6/metabolism*
- Wnt Proteins/antagonists & inhibitors
- Wnt Proteins/metabolism
- Endocytosis*/drug effects
- Embryo, Nonmammalian/metabolism
- Humans
- beta Catenin/metabolism
- Zebrafish/growth & development
- Zebrafish/metabolism
- Glycosylation
- Cell Line
- PubMed
- 32649905 Full text @ Cell Chem Biol
Citation
Hong, S., Feng, L., Yang, Y., Jiang, H., Hou, X., Guo, P., Marlow, F.L., Stanley, P., Wu, P. (2020) In Situ Fucosylation of the Wnt Co-receptor LRP6 Increases Its Endocytosis and Reduces Wnt/β-Catenin Signaling. Cell chemical biology. 27:1140-1150.e4.
Abstract
Wnt/β-catenin signaling regulates critical, context-dependent transcription in numerous physiological events. Among the well-documented mechanisms affecting Wnt/β-catenin activity, modification of N-glycans by L-fucose is the newest and the least understood. Using a combination of Chinese hamster ovary cell mutants with different fucosylation levels and cell-surface fucose editing (in situ fucosylation [ISF]), we report that α(1-3)-fucosylation of N-acetylglucosamine (GlcNAc) in the Galβ(1-4)-GlcNAc sequences of complex N-glycans modulates Wnt/β-catenin activity by regulating the endocytosis of low-density lipoprotein receptor-related protein 6 (LRP6). Pulse-chase experiments reveal that ISF elevates endocytosis of lipid-raft-localized LRP6, leading to the suppression of Wnt/β-catenin signaling. Remarkably, Wnt activity decreased by ISF is fully reversed by the exogenously added fucose. The combined data show that in situ cell-surface fucosylation can be exploited to regulate a specific signaling pathway via endocytosis promoted by a fucose-binding protein, thereby linking glycosylation of a receptor with its intracellular signaling.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping